Mechanistic Models of Neurodegenerative Disorders
Poster #201: Alice Mukora
Title: Sex-specific signatures of dementia risk factors and the impact of reproductive aging in females
Abstract: Treating modifiable dementia risk factors—such as obesity, hypertension, and metabolic disorders—may delay or prevent maladaptive neurodegeneration. Research has shown that these factors impact males and females differently, prompting investigation into sex-specific dementia risk profiles. In females, the risk of cognitive decline increases after menopause, a period linked to structural brain changes, particularly in regions involved in higher cognitive functions. In this study, we examined sex-specific relationships, including menopause, between dementia risk factors and brain structure in age-matched cohorts. Using the UK Biobank, we analyzed data from 28,636 participants (ages 45–82; 50.4% female), including modifiable risk factors and regional cortical thickness derived from T1-weighted MRI scans. Partial Least Squares (PLS) analysis was conducted separately by sex to identify latent variables (LVs) capturing brain-behavior covariance. We found five significant LVs in females and four in males (p < 0.05). LV2 in both sexes showed similar cortical thickness patterns but differed behaviorally, particularly in relation to exercise and education. Stratifying females by menopausal status (premenopausal, postmenopausal, and surgical menopause) revealed distinct brain-behavior profiles. A sub-analysis of age-matched females by menopausal group identified one significant LV, explaining 60.89% of covariance, linked to widespread cortical thickening, disturbed sleep, and elevated blood pressure. A repeated analysis including age-matched males found one LV explaining 59.84% of covariance, associated with cortical thickening and increased household size. These findings highlight the nuanced, sex-specific relationships between brain structure and modifiable dementia risks, emphasizing the need for tailored prevention strategies that consider sex and menopausal status.
Poster #202: Amelie Metz
Title: Divergent trajectories of atrophy and White Matter Hyperintensities in Frontotemporal Dementia subtypes
Abstract: Frontotemporal Dementia (FTD) includes subtypes with varying symptoms and pathological changes. However, the longitudinal progression of subcortical atrophy and white matter hyperintensities (WMH), along with their distinct effects on cognitive domains across FTD subtypes, remains largely unexplored. Deformation-based morphometry (DBM), a neuroimaging technique with enhanced sensitivity to subcortical changes, provides a valuable tool for investigating neurodegeneration. This study therefore examined subtype-specific brain atrophy, estimated via DBM, alongside WMHs, and their associations with cognitive impairment in FTD. Longitudinal MRI and cognitive data from 136 FTD patients (70 behavioral-variant FTD [bvFTD], 36 semantic-variant primary progressive aphasia [svPPA], 30 nonfluent-variant PPA [nfvPPA]) and 133 healthy controls were analyzed. Linear mixed-effects models were used to compare atrophy patterns and WMH load between patients and controls, as well as across FTD subtypes. Atrophy and WMH patterns were then linked to behavioral scores. In bvFTD, atrophy was prominent in the frontal cortex; in svPPA, in temporal areas and the hippocampus; and in nfvPPA, in the basal ganglia. WMH volume, while more pronounced in bvFTD, followed a similar pattern across subtypes, being more prevalent in the left-hemispheric and anterior regions. Cognitive impairments were differentially associated with these pathological changes across the subtypes. This study provides further insight into disease mechanisms in FTD by showing that neurodegeneration and WMHs contribute differentially to impairments in different cognitive domains. We also emphasize the utility of DBM in the study of neurodegenerative disorders by highlighting the involvement of subcortical atrophy and ventricular expansion in FTD.
Poster #203: Antoine Bou Khalil
Title: Bilateral Cortical Activity in Congenital Mirror Movement Syndromes
Abstract: Congenital Mirror Movement (CMM) is a rare syndrome where any voluntary movement of a limb is simultaneously accompanied by an unvoluntary, mirrored movement of the opposite limb. The involuntary movements mostly affect the upper extremity of the body, particularly the hands and fingers. This condition therefore causes considerable manual dexterity impairments. While CMM is caused by mutations in multiple genes, genotype-phenotype associations have yet to be fully determined. One major hypothesis suggests that CMM results from abnormal bilateral corticospinal tract projections, where each motor cortex has both a normal crossed projection to the opposite limb and an abnormal uncrossed projection to the same-side limb. However, other hypotheses suggest a cortical cause. We conduct the first neurophysiological characterization of CMM using magnetoencephalographic imaging (MEG) to identify dynamics of atypical bilateral cortical activity during unilateral motor tasks and tactile stimulation in CMM patient participants. Our pilot results confirm that bilateral motor and premotor cortical activity occurs with finger movements, whereas tactile stimulation evokes typical contralateral activation. This demonstrates that involuntary movements of the ipsilateral limb involve the contralateral pre/motor cortex, suggesting that mirror movements are not solely due to abnormal uncrossed corticospinal projections. Time-resolve imaging refines our understanding of the brain dynamics underlying a disorder with clear behavioral elements such as CMM, advancing a broader comprehension of motor control.
Poster #204: Atchaya S. Kanagasabai
Title: Morphological and Functional Dysfunctions of Mitochondria in the Cerebellum of the Christianson Syndrome Mouse Model.
Abstract: Christianson Syndrome is a neurological disorder where ataxia, characterized by motor incoordination, is among the most debilitating symptoms. Currently, there is no cure available for this rare ataxia, despite its grave impact. Christianson Syndrome shows an intriguing cell death pattern where Purkinje cells, the primary output cells in the cerebellum, exhibit selective vulnerability. Purkinje cells in the anterior region are particularly susceptible to cell death, while those in the posterior region remain resilient, despite being exposed to the same genetic insult. Anterior Purkinje cells fire at higher frequencies and, consequently, require a higher energy demand than those in the posterior, suggesting energy-related issues may contribute to cell death in Christianson Syndrome. Using RNAseq and DESeq2 analysis, we identified several gene families regulating mitochondria as highly dysregulated in the vulnerable anterior cerebellum of Christianson Syndrome mice. Therefore, we hypothesize mitochondrial dysregulation in anterior Purkinje cells may contribute to their vulnerability. Using electron microscopy, we demonstrate a significantly increased number of damaged mitochondria and a significantly decreased number of mitochondria in anterior Purkinje cells of Christianson Syndrome mice. We also show changes in mitochondrial function by immunohistochemistry in both live and fixed cerebellar slices. Our findings suggest that mitochondrial dysfunctions may be a novel therapeutic target for Christianson Syndrome.
Poster #205: Benjamin Rogers
Title: Clocking in on ataxia: Per2 dysregulation in the cerebellum of spinocerebellar ataxia type 6 (SCA6) mice
Abstract: Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative disorder that leads to the progressive loss of motor coordination and cerebellar dysfunction. While the hallmark of SCA6 is motor, sleep disturbances are increasingly recognized as a prevalent occurrence in patients. Sleep disturbances significantly impact quality of life and well-being of these patients. However, the relationship between sleep disorders and the underlying pathological mechanisms driving ataxia in SCA6 remains unclear. Interestingly, recent studies have identified that the clock genes are rhythmically in the cerebellum throughout the light-dark cycle. This prompted us to examine the expression of clock genes in the cerebellum of male and female SCA6 and litter-matched wild-type (WT) mice. We observed a reduction in the expression of Per2 in the cerebellum at zeitgeiber time (ZT) 10 without any significant changes in other clock genes. Expression was largely limited to cerebellar Purkinje cells, the principal cells of the cerebellum that are affected in SCA6. Furthermore, SCA6 mice demonstrate impaired running wheel activity during the transition from the light to dark phase at ZT10. We believe that by understanding the dysregulation of clock genes in the cerebellum of SCA6, we will gain valuable insights into non-motor dysfunction and may also identify novel therapeutic strategies to address both motor and non-motor symptoms in SCA6, that may also have implications for other forms of ataxia.
Poster #206: Caitlin Atkinson
Title: Development of a gene therapy for Autosomal Recessive Spastic Ataxia of the Charlevoix-Saguenay using a miniconstruct of sacsin
Abstract: Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay is a rare, early onset neurodegenerative disease characterized by a common triad of symptoms that include ataxia, muscle stiffening, and peripheral neuropathy. ARSACS is caused by mutations in the SACS gene, resulting in the dysfunction and downregulation of sacsin, a large multimeric protein enriched in neurons. Previous studies assessing the structures of sacsin domains have indicated that sacsin may function as a protein chaperone, assisting in protein folding and quality control. In ARSACS, sacsin dysfunction may disrupt the structure and functions of sacsin’s binding partners. To date, there is no cure or treatment for ARSACS that effectively targets the cause of the disease. In this study, we have developed a miniconstruct of sacsin, known as “minisacsin”, that can be packaged into a viral vector to replace the function of sacsin. We have shown that minisacsin treatment in neonatal Sacs-/- mice (a murine model of ARSACS) delays symptomatic behaviour and disease progression. Treatment to cell culture models suggests restored sacsin function through the resorption of ARSACS molecular markers. The next step of this project includes treating symptomatic Sacs-/- mice to assess the efficacy of minisacsin in resolving ataxic symptoms after the onset of ARSACS.
Poster #207: Cathy Fang
Title: Understanding Cognitive Impairment in Early Psychosis through Functional Brain Dysconnectivity: A Whole-Brain Analysis Approach
Abstract: Early psychosis (EP) is the early stage of onset of psychosis symptoms, characterized by a loss of touch with reality. Cognitive impairment is prominent and even precedes symptom onset in individuals with psychosis, which is commonly driven[ma2] by alterations in functional brain connectivity. Previous work has focused on brain regions defined a priori and relied on the assumption of normal distributions, which can hinder result generalizability. This project aims to build upon previous findings in a data-driven way and share code following open science principles. We utilize the Human Connectome Project-Early Psychosis dataset of 183 participants consisting of resting-state functional magnetic resonance imaging (rs-fMRI) scans and phenotypic data of a variety of cognitive domains, such as attention, memory and processing speed. Functional connectivity is calculated based on Schaefer 400 parcellations to derive voxel-whole brain connectivity patterns. Multivariate Distance Matrix Regression (MDMR), a non-parametric technique, is then applied to assess relationships between functional connectivity differences and cognitive scores. Statistics for hypothesis testing follow an asymptotic null distribution, and theoretical p-values can be calculated to make the results more robust. Further, scripts detailing the data analysis will be shared on GitHub, linked to an Open Science Framework project to aid replicability. We expect to identify some well-known brain areas implicating specific impairments, which will be externally validated in a follow-up study. This may provide a holistic view of brain-cognition relationships for early psychosis and guide future applications in other fields of research.
Poster #209: Delphine Oliva-Lopez
Title: Enhancing Plasma Biomarker-Based Detection of Tau Pathology with Cognitive Screening in Alzheimer’s Disease
Abstract: Introduction: Tau-PET imaging is the gold standard for monitoring Alzheimer’s disease (AD) progression, but it is costly and not widely accessible. Plasma biomarkers such as pTau181, pTau217, and pTau231 offer promising alternatives, with pTau217 showing strong associations with cognitive decline and tau accumulation. However, their effectiveness in predicting tau-PET positivity when combined with cognitive measures remains unclear. This study evaluates whether integrating MoCA scores with plasma pTau biomarkers improves the identification of tau pathology in AD-related regions, specifically the MetaROI. Methods: We analyzed 139 participants (16 AD, 22 MCI, 101 CN), classifying them as Tau+ (n = 48) or Tau− (n = 91) based on [¹⁸F]MK-6240 PET-SUVR thresholds set at 2.5 SD above the CN mean in the MetaROI. Plasma pTau181, pTau217, and pTau231 were log-transformed, and multicollinearity was assessed. MoCA scores were analyzed by total and subscores (Memory, Orientation, Attention, Semantic, Visuospatial), with MMSE used for validation. Logistic regression and ROC curve analyses were performed to assess classification performance in R and Python. Results: pTau217 was the strongest standalone predictor of tau-PET positivity, independent of cognitive scores. In contrast, combining MoCA Memory and Orientation subscores significantly improved the predictive performance of pTau181 and pTau231, outperforming the MoCA total score but still not exceeding the accuracy of pTau217 alone. Conclusion: Plasma pTau217 reliably predicts MetaROI tau pathology without cognitive input. However, MoCA Memory and Orientation scores enhance the utility of pTau181 and pTau231, supporting a multimodal approach to improve early detection and reduce reliance on PET imaging in AD-spectrum populations.
Poster #210: Diana Casas
Title: A patient-derived microglia model to study glial interactions and develop targeted therapies
Abstract: Adult leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare neurodegenerative white matter disease caused by heterozygous pathogenic variants in the colony-stimulating factor 1 receptor gene (CSF1R). CSF1R is a key receptor expressed by microglia, the primary immune cell of the central nervous system, where CSF1R signaling is critical for proliferation, survival, and function of microglia. Without appropriate CSF1R signaling, microglia become highly cytotoxic and drive pathology of the surrounding tissue, including loss of oligodendrocytes and neuronal damage. In ALSP, microglial activation is driven by the dysregulation of CSF1R expression, thereby inducing increased inflammation, contributing to neurodegeneration and white matter loss. Understanding how CSF1R variants affect the development and function of microglia will allow us to 1) better understand the high intersubject clinical heterogeneity observed in ALSP, 2) lay the foundation for identifying potential therapeutic options for treating ALSP, and 3) generate a robust disease model to investigate microgliopathies. We derived microglia from ALSP patients and showed that mutated microglia have a higher phagocytic activity towards myelin and a different cytokine after activation. To repair these microglia, we are leveraging the capabilities of nanoparticles to deliver cargo to cells in hopes of rescuing a healthy phenotype. We anticipate that human ALSP microglia can efficiently and specifically uptake and process nanoparticles for the delivery of CSF1R mRNA to reverse cytotoxic effects of these cells sufficiently. We aim to determine toxicity, specificity, and longevity of therapies on ALSP cells to inform further product development that is critical for translation.
Poster #211: Fahed El-Khaldi
Title: Self-reported word-finding difficulties: A potential early marker of amyloid positivity in cognitively unimpaired older adults.
Abstract: Word finding difficulties (WFD) among cognitively healthy older adults rank as one of the most prevalent and severe complaints, matching or surpassing memory related complaints. These cognitive complaints are often overlooked and typically dismissed as a normal part of aging. However, recent research suggest that subjective WFD predicts cerebrospinal fluid amyloid levels and may serve as an early indicator of Alzheimer’s disease (AD), even before more widely recognized symptoms appear. This study investigates the relationship between self-reported WFD and established AD biomarkers i.e amyloid positivity in cognitively unimpaired older adults. This project introduces a newly developed questionnaire that solely assesses WFD to grasp a comprehensive picture of the severity and frequency of WFD. Results show significant associations between WFD and amyloid positivity, supporting the hypothesis that these subjective complaints may reflect underlying neuropathology. These findings highlight the potential utility of WFD as an early, accessible marker for AD risk, highlighting the importance of incorporating subjective complaints into clinical assessments of cognitive health.
Poster #212: Guofeng Ye (Trainee Flash Talks)
Title: Effects of Non-Invasive Brain Stimulation on Beta Oscillations During Hand Movement in Stroke Individuals
Abstract: After a stroke, more than half of individuals experience motor impairment, significantly affecting their quality of life. Using electroencephalography (EEG), brain oscillatory features such as Movement-related beta desynchronization (MRBD) have been shown to be associated with motor function. In stroke, lower baseline resting beta power and reduced MRBD were reported in the ipsilesional primary motor cortex (M1), where lower values were associated with greater motor impairment. While non-invasive brain stimulation (NIBS) like transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) show promise in modulating MRBD and enhancing motor performance in healthy individuals, their effects on beta oscillatory patterns are yet to be investigated in the context of stroke, which was the goal of this study. EEG signals were collected from 10 stroke individuals and 15 healthy aging subjects. Three types of NIBS were tested in 4 stroke individuals: high-density (HD) 2mA tDCS, 1mA HD 70Hz tACS, or sham NIBS. NIBS was applied over the ipsilesional M1 while participants performed handgrips with the contralateral hand. EEG signals were collected before, as well as 15- and 45-minutes post NIBS and compared to those of the control group. Preliminary results show that stroke individuals had lower baseline beta power (64%) compared to the control group. Anodal tDCS increased the depth of the MRBD (49% post-15min, 96% post-45min), while 70Hz tACS decreased it (-46%, -52%). Understanding how NIBS modulates brain patterns is crucial for developing effective rehabilitation strategies. This study will contribute to developing personalized stimulation protocols post-stroke.
Poster #213: Houman Azizi
Title: Genetic Architecture of Parkinson’s Disease: Investigating the Relationships Between Pathway-Specific Polygenic Risk Scores and Neuroanatomical Features
Abstract: Parkinson’s disease (PD) is associated with genetic risk factors and brain structural alterations. How these genetic factors influence brain anatomy and contribute to disease risk remains unclear. Here, we aimed to characterize neuroanatomical correlates of PD genetic risk and differentiate between factors affecting neurodevelopment versus those contributing to later-life PD vulnerability. Associations between polygenic risk scores of PD (PD-PRS) and brain measures were examined using linear regression, and their potentially causal relationships were investigated through Mendelian randomization. Next, PD risk genes were stratified based on their functions and their neuroanatomical associations were assessed. Finally, we investigated the developmental gene expression trajectories of each pathway using RNA-sequencing data and compared them to the expression patterns of other PD risk genes. PD-PRS showed widespread positive associations with cortical SA, subcortical volumes, and white matter FA. Mendelian randomization revealed increased cortical SA and larger subcortical volumes to have a potentially causal effect on PD development. However, similar associations were not observed between lysosomal, autophagy, or mitochondrial pathway-specific PD-PRSs and brain structural measures. Developmental gene expression trajectory analyses revealed distinct patterns of expression for all pathway-specific genes, showing significantly lower expression during fetal stages compared to other PD risk genes. Our findings link PD genetic risk to brain structure, suggesting greater gray matter size and white matter integrity may increase PD risk. The lower fetal expression of pathway-specific genes, along with lack of associations with neuroanatomical features, suggests these pathways may contribute to disease risk through mechanisms independent of early neurodevelopment.
Poster #214: Hunter Murdoch
Title: Role of mitotic senescence of NG2-glia in remyelination impairment in multiple sclerosis.
Abstract: Multiple Sclerosis (MS) is a neurodegenerative autoimmune disease characterized by immune-mediated demyelinating insults that cause neurological disability. NG2-glia are the principal oligodendrocyte progenitor cells in the CNS, positioning them as crucial players in the remyelination process. The NG2-glia population is maintained solely through self-renewing divisions, but their proliferative capacity is not unlimited and diminishes with age. My project aims to establish a correlation between the ‘mitotic age’ of NG2-glia and their ability to proliferate and differentiate into new myelinating oligodendrocytes (OLs). Given the increased turnover of NG2-glia in MS, I hypothesize that the resulting accelerated mitotic aging impairs their ability to produce new myelinating OLs and thus exacerbates MS. To mimic the increased NG2-glia turnover seen in MS, I utilized a novel paradigm to artificially increase the mitotic age of NG2-glia in the absence of substantial effects on other neural cell lineages. These artificially aged NG2-glia resemble those seen in established MS models and natural aging. Additional work is underway to further characterize this response and assess its effect on remyelinating processes. This work will provide us with a better understanding of NG2-glia in aging and disease and may lead to the development of NG2-glia-focused therapeutics that could slow or halt MS progression. This work is supported by funding from the Canadian Institutes of Health Research, Research Institute of the McGill University Health Centre, and Healthy Brains, Healthy Lives.
Poster #215: Ishana Rue
Title: Longitudinal changes in serum neurofilament light in primary psychiatric disorders
Abstract: Introduction: Serum neurofilament light (sNfL) is a biomarker of neurodegeneration which differentiates neurodegenerative diseases such as frontotemporal dementia (FTD) from primary psychiatric disorders (PPD). However, sNfL is also slightly higher in PPD compared to healthy controls. The reason for this elevation is unclear, and it is unknown whether this difference persists over time, or if it is related to disease severity. This study explores longitudinal sNfL in PPD patients. Methods: Longitudinal serum samples and clinical data from PPD patients (ages 40+) were obtained from the Biobanque Signature at up to four time points over one year (from ER visit to discharge and outpatient follow-up). sNfL was measured using SiMoA assay technology. We conducted a repeated measures analysis to test sNfL change over time, adjusting for age, BMI, and blood creatinine. Sex and gender were entered as factors and examined as interactions with time. Results: The study included 268 subjects with at least 2 timepoints (males =135, females=133), and 73 subjects with 4 timepoints (males=32, females=41). We did not detect a significant change of sNfL over time. Males had slightly higher sNfL than females. Interactions between sex/gender and time were not significant. Conclusion: This study did not detect a significant change in sNfL in PPD patients over 1 year. These results suggest that the mild elevation observed in PPD is a disease trait rather than disease state dependent. Future analyses will investigate the correlation between sNfL and measures of psychiatric disease severity over time.
Poster #216: Jacky Chen
Title: Partial Retinal Stimulation Analysis of the Optokinetic Response reveals equivalent functional contributions from cortical and subcortical pathways
Abstract: Human infants, as well as many animals with laterally placed eyes and restricted binocular vision, showing a prominent naso-temporal asymmetry in their optokinetic responses (OKR) to motion fields: horizontal temporo-nasal motion (towards the nose) elicits much larger optokinetic responses than horizontal naso-temporal motion (towards the sides). In humans, this asymmetry usually disappears during development, but remains present if binocular vision is impaired (for example, in infant strabismus). The emergence of a symmetric optokinetic response is believed to result from the emergence of an indirect retino-cortico-pretectal pathway, but this is based on indirect evidence. Here, for the first time to our knowledge, we use spatially localized motion fields stimulating either the nasal or temporal retina to selectively activate distinct neural circuits involved in OKR generation. When measuring the optokinetic responses when viewing monocularly (with either eye) or binocularly, our preliminary data show that in adults with normal vision, OKRs driven by motion signals flowing through a pathway that ascends to the cortex before descending to the midbrain on either side are equal in potency to those that can additionally flow through a direct pathway from the retina to the midbrain. The results shed light on the intriguing connection between OKR and the normal development of binocular vision as well as its breakdown in strabismus. They may support the future development of targeted strategies for visual rehabilitation in patients with disrupted ocular alignment.
Poster #217: Janice Park
Title: Leveraging multiple disease epicenters and machine learning to refine neurodegeneration-based disease staging in a mouse model of synucleinopathies
Abstract: Alpha-synuclein (αSyn) spreading is a pathological hallmark of Parkinson’s Disease (PD) progression. Recent studies using mouse models receiving intracerebral αSyn inoculation demonstrated this empirically. However there are different known disease epicentres (brainstem; olfactory bulb) that yield the same clinical phenotypic abnormality. Here, we use Subtype and Stage Inference Algorithm (SuStaIn), a machine-learning tool developed to define clinical subtypes based on similarity in disease trajectory, to test to what extent distinct brain atrophy pathways originating from different experimentally-induced “disease epicenters” converge and diverge throughout disease progression. 11 week-old M83 hemizygous mice overexpressing A53T αSyn were injected with 2.5 μL saline (PBS) or pre-formed αSyn fibrils (PFF) into the right dorsal striatum highly implicated in PD, or hippocampus, a non-traditional disease epicenter (n=~8 inoculum/injection site/sex/timepoint). Mice underwent in vivo T1-weighted MRI at -7, 30, 90, and 120 days post-injection. Using deformation-based morphometry, we observed vastly different brain atrophy patterns from each disease epicenter, yet evidence of motor deficits were observed in both groups. We jointly analysed MRI data from both disease epicenters and calculated volumetric changes for 9 brain regions of interest relative to pre-injection data (n~192 images) normalized by timepoint-matched controls as SuStaIn inputs. SuStaIn revealed a hippocampus-first subtype, which unsurprisingly consist of hippocampal PFF-injected mice, while the striatal PFF-injected mice were split into two diverging subtypes: the nigrostriatal-first, and the motor-corticostriatal-first. Leveraging a data-driven approach in a mouse model, our results demonstrate that heterogeneity in synucleinopathy progression is not only epicenter-specific, but also subject-specific.
Poster #218: Jiakang Tian
Title: Mapping synaptic connections with a novel synthetic Notch receptor approach
Abstract: Understanding how genetically defined neural circuits drive specific behaviors is crucial for neuroscience and the development of targeted therapies for neurological disorders. While existing neuronal circuit tracers are effective, they lack the ability to anterogradely label distinct postsynaptic populations that receive inputs from genetically defined presynaptic populations. Here, we introduce Transsynaptically-Induced Recombinase-Activated Neuron Tracing (TIRANT), a novel transsynaptic labeling tool that enables the expression of a recombinase in postsynaptic neurons receiving input from a genetically specified presynaptic population. TIRANT employs a synthetic ligand expressed in presynaptic neurons and a synthetic Notch receptor fused to a recombinase in postsynaptic neurons. Ligand-receptor binding triggers cleavage of the intracellular domain, releasing the functional recombinase and enabling genetic labeling of connected neurons. We modulated the synthetic Notch receptor by adding additional modular components to the extracellular and intracellular domains. Using AAV-mediated delivery, we demonstrate ligand-dependent activation of the receiver construct. As proof of concept, we injected the Notch construct into the striatum and the ligand construct into the VTA, successfully inducing FLP recombinase expression in striatal neurons receiving VTA input. This approach provides a precise and versatile strategy for mapping neuronal connectivity with genetic specificity, as well as offering options to manipulate the neuronal circuits by expressing recombinase constructs, advancing circuit-tracing methodologies.
Poster #219: Jiayue Yang
Title: Characterizing the effects in resting-state MRI, touchscreen tasks, and activity monitoring in synucleinopathy marmosets
Abstract: The number of Canadians at risk of Parkinson’s disease (PD) has been sharply increasing due to global aging. Despite decades of research, a complete cure for PD has yet to be found, and rodent models often fail to translate to human trials. To bridge this gap, we implement the common marmoset (Callithrix jacchus), a non-human primate (NHP) model closer to humans, to study PD mechanisms and improve therapy development. By injecting preformed fibrils (PFF) to trigger alpha-synuclein (alpha-syn) spreading, we aim to model PD-like behavioral and cognitive deficits. This study integrates awake resting-state magnetic resonance imaging (MRI), structural MRI, touchscreen tasks, and activity measures to identify neural correlates of altered brain networks in PD. Marmoset behavior is monitored using actigraphy watches and pose estimation software (DeepLabCut and YOLO). We hypothesize that connectivity changes will emerge around nine months post-PFF injection, reflected in coordinated BOLD responses near injection sites. We predict reduced activity levels and touchscreen performance due to dopaminergic fiber loss and altered neural signaling. A cohort of 3 marmosets (2 males, 1 female) has baseline data collected, with post-injection MRI, touchscreen, and activity data to be gathered bimonthly. This longitudinal study aims to identify biomarkers of toxic alpha-syn aggregate spreading (synucleinopathy), providing insights into PD progression and facilitating the development of targeted therapies. This approach leverages advanced imaging and behavioral tools to improve translational research and address the limitations of current models.
Poster #220: Julia Tourbina
Title: Investigating the possible cause of Purkinje cell firing deficits and death in Christianson syndrome ataxia
Abstract: One characteristic of Christianson syndrome (CS), rare X-linked neurological disorder, is ataxia, a locomotor disorder often caused by cerebellar damage. Death of Purkinje cells (PCs), main cerebellar pacemaker cells, is a hallmark of ataxia. In many ataxias, PC firing deficits precede PC death. In our CS mice, we observe PC death only in the anterior cerebellum starting on post-natal day (p)35, but it is unknown if firing deficits occur before. Using loose-patch recordings and synaptic blockers, we found intrinsic PC firing deficits only in the anterior in CS mice at p35, but not p25. A hypothesis in the field is that rescuing PC firing deficits can prevent motor deficits. To understand the cause of these firing deficits in CS in the anterior, RNA sequencing was done at p60, at ataxia onset, comparing WT and CS mice. One major finding was a decrease in beta subunit 4 of sodium channels (Scn4b). It is known that knocking out Scn4b in mice is sufficient to reduce PC firing rates and cause ataxia. We hypothesized that reduced Scn4b protein levels in the anterior cerebellum lead to anterior PC firing deficits, cell death and ataxia in CS mice. We validated RNAseq by showing decreased Scn4b mRNA in the anterior at p60, and Scn4b protein decrease only in the anterior cerebellum at p35 and p60, but not p25 suggesting a role in PC firing deficits. These data suggest that Scn4b could be a novel therapeutic target for CS gene therapy.
Poster #221: Katherine Chadwick
Title: The Utility of White Matter Hyperintensities as a Biomarker in Amyotrophic Lateral Sclerosis
Abstract: While sclerosis of the corticospinal tract is a key pathological feature of Amyotrophic Lateral Sclerosis (ALS) and previous work in the context of other neurodegenerative diseases has established white matter hyperintensities (WMHs) as magnetic resonance imaging (MRI) markers of white matter damage and disease progression, WMHs remain unexplored in ALS. The present work investigates the relationship between presence and progression of WMHs and disease severity and survival in ALS patients. We included longitudinal MRI and clinical data of 232 ALS patients and 207 matched controls from the Canadian ALS Neuroimaging Consortium (CALSNIC) (Kalra et al. 2019). T1-weighted and FLAIR MRIs were used to perform WMH segmentation using BISON pipeline (Dadar et al. 2021). Linear mixed effect modeling was employed to investigate the differences in WMH burden and longitudinal progression between the ALS patients and matched controls, and to assess the relationship between WMH progression and disease severity as measured by ALSFRS-R. Age and sex were considered as covariates and participant IDs as random effects. Compared to healthy controls, ALS patients had significantly greater template-averaged longitudinal WMH progression (911.5 mm3/year, p < 0.0001). Moreover, for every 500 mm3 increase in template-averaged WMH volume, the ALSFRS-R scores decreased by a full point (p < 0.001). This study has shown, for the first time, that ALS patients present with greater WMH progression, and that WMH progression is linked to disease severity and survival in patients, highlighting the utility of WMH as a biomarker of disease progression and prognosis in ALS.
Poster #222: Lina Sifi
Title: Ovariectomy in Mice Induces Transient Structural Brain Changes with Full Recovery Over Time
Abstract: Menopause, occurring through natural endocrine ageing or clinical interventions, is a universal experience that leads to reproductive senescence in women. While menopause is a normal endocrine transition, it is associated with neurological symptoms, reduced quality of life, and increased risk of neurodegenerative disorders. Yet, the long-term effects of menopause on the brain remain poorly understood. Here, we utilized the ovariectomized mouse model to replicate key features of human menopause and assessed voxel-wise volumetric changes longitudinally using T1-weighted magnetic resonance images (MRI; 100 μm³ voxels, Bruker 7T), with age-matched females serving as controls (n=97). Using voxel-wise deformation morphometry, the results revealed decreased brain volume in ovariectomized mice between 30 and 60 days post-surgery, particularly in focal regions such as the left thalamus, midbrain, and anterior olfactory nucleus. However, these effects were reversed, with brain volume fully recovering 90 days post-surgery. We also examined circulating pituitary gonadotropin hormone levels using enzyme-linked immunosorbent assay. Consistent with previous literature, we found elevated luteinizing hormone and follicle-stimulating hormone levels in ovariectomized mice, reflecting decreased estrogen levels (not measured). These hormonal changes are analogous to those seen in human post menopause. Our results align with human studies demonstrating that gray matter volume and cognitive function often recover post-menopause, suggesting adaptive compensatory mechanisms. These findings highlight the importance of understanding the mechanisms underlying brain recovery post-menopause to improve women’s quality of life. Future research should explore if the rapid change after ovariectomy represents a possible critical period relative to exposures to risk factors for maladaptive ageing.
Poster #223: Mikael Nakamura Vernet
Title: Altered neuronal excitability during development affects long-term social behaviour and interneuron circuitry in mice
Abstract: Comorbidity is frequent between epilepsy and autism spectrum disorder (ASD), with 30% of children diagnosed with autism having experienced seizures and vice versa. Previous rodent studies have demonstrated that induced early-life seizures (ELS) can lead to social impairments, but little is known about the neuronal mechanisms underlying this impairment. We investigated whether increased neuronal excitability during critical periods of neonatal brain development affects social behaviour. The chemoconvulsant pentylenetetrazol (PTZ), a GABAA receptor antagonist, was injected into wild-type mice at the minimum convulsive dose of 50 mg/kg. Injections were performed once daily during a critical window of cortical circuitry development from P8-11. To confirm whether PTZ induces hyperactivity during this period, mice were perfused and immunostained for c-Fos-a marker of neuronal activity. Compared to saline-injected controls, PTZ-injected mice exhibited increased c-Fos+ cells in the mPFC, ACC, and striatum. To observe if social impairments are caused by hyperactivity during the critical period, the three-chamber test was performed at P30. Behaviours were assessed with a custom-made supervised animal-tracking algorithm on DeepLabCut. PTZ-injected mice displayed reduced social preference. We are currently leveraging the supervised machine learning platform SimBA, for automated detection of social behaviour. Since maturation of PVINs occurs during a critical window that coincides with the PTZ injections, hippocampal PVIN density and perineuronal net (PNN) expression was investigated. Preliminary data indicate a decrease in PNN density. Altogether our results demonstrate that increased neuronal activity in critical periods of neonatal development impairs social behaviour and affects PNN density.
Poster #224: Naama Brezner
Title: DNA Methylation in Astrocyte Maturation
Abstract: The molecular mechanisms controlling astrocyte specification have been intensely investigated, with emerging studies indicating the involvement of epigenetic modifications, including DNA methylation. In contrast, little is known about mechanisms controlling the later developmental step, where immature astrocytes develop into mature adult astrocytes. During maturation, astrocytes undergo molecular, structural, and functional changes required for adult physiological functions. A recent study found that chromatin remodeling occurs during maturation, raising the question of whether DNA methylation is also involved. An increased ratio of 5-hydroxymethylcytosine (5-hmC) to 5-methylcytosine (5-mC) methylation in the brain correlates with higher gene expression levels. My research focuses on comparing DNA methylation patterns between immature (early postnatal) and mature astrocytes in mice. Using immunolabelling, I compared the 5-hmC to 5-mC ratios in astrocytes from adult and P14 mouse dentate gyrus. In P14 brains, granule layer astrocytes exhibited a lower 5-hmC/5-mC ratio compared to molecular layer astrocytes, a difference absent in adult brains. Since granule neurons are known to mature later in postnatal development, it is possible that dentate astrocytes remain in an immature or alternate state. This provides initial evidence of dynamic DNA methylation changes during astrocyte maturation. Future work will explore 5-hmC/5-mC ratios in other brain regions and sequence methylation sites to map changes to specific genes. Additionally, I plan to knock down DNA methyltransferases (DNMTs) to assess their role in astrocyte maturation. I hypothesize that astrocytes rely on alterations in DNA methylation to drive gene expression changes needed for maturation and that DNMT knockdown will hinder this process.
Poster #225: Parsa Khalafi
Title: Data-Driven Subtyping of α-Synuclein Neuropathology Uncovers Spinal Cord-Mediated Pathways and Clinico-Pathological Heterogeneity in Synucleinopathies
Abstract: Synucleinopathies, characterized by α-synuclein (αSyn) aggregation, exhibit heterogeneous progression patterns that challenge existing neuropathological frameworks. Applying the Ordinal Subtype and Stage Inference (SuStaIn) algorithm to a population-based autopsy cohort, this study identified three distinct spatiotemporal progression subtypes of αSyn pathology: (1) Olf-Amy (limbic-predominant), initiating in olfactory regions and progressing to the amygdala and limbic system, (2) Olf-Brainstem (brainstem-predominant), advancing from olfactory to brainstem nuclei with subsequent cortical involvement, and (3) DMV-IML (spinal-predominant), originating in the dorsal motor nucleus of the vagus and spinal intermediolateral column, ascending to the brain while exhibiting preferential spinal/peripheral pathology. Each subtype demonstrated unique pathological and clinical profiles: Olf-Amy showed pronounced Alzheimer’s disease–related amyloid-β and tau pathology, higher APOE-ε4 prevalence, and severe dementia, Olf-Brainstem aligned with dementia with Lewy bodies neuropathological criteria, and DMV-IML featured early peripheral nervous system involvement. αSyn pathology burden independently predicted cognitive decline, with higher brain-stage progression linked to worse cognitive scores, even after adjusting for AD co-pathology. By integrating spinal cord regions, the study uncovered bidirectional peripheral-central propagation pathways, challenging traditional brain-centric models. These findings highlight the utility of data-driven models in resolving synucleinopathy heterogeneity, emphasize subtype-specific diagnostic implications, and validate spinal cord pathology as a critical biomarker for early disease mechanisms.
Poster #226: Platon Megagiannis (Trainee Flash Talks)
Title: Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes
Abstract: Neuroinflammation plays a central role in the progression of various neurodegenerative disorders, such as in Alzheimer’s disease. Recent evidence points to excessive neuroinflammation contributing to disease exacerbation and pathophysiological deterioration in these disorders. Glial cells, particularly astrocytes and microglia, are major mediators of neuroinflammation, responding to inflammatory stimuli in a process termed reactive gliosis. Contemporary research has highlighted reactive gliosis as a potential therapeutic target for neurodegenerative diseases. Understanding the molecular and cellular mechanisms underlying neuroinflammation is critical for developing strategies to modulate gliosis and improve disease outcomes. In this study, we demonstrate that the ASD-associated chromatin remodeler CHD8 regulates the brain’s inflammatory response through its activity in astrocytes. We show that global deletion of the Chd8 gene in adult mice impairs reactive gliosis. Conditional Chd8 deletion specifically in astrocytes—rather than in microglia—suppresses reactive gliosis by inhibiting astrocyte proliferation and morphological changes in a stab-wound injury model. Furthermore, astrocyte-specific Chd8 ablation reduces LPS-induced neuroinflammation, conferring protective effects in mice. Gene expression profiling and ATAC sequencing reveal that Chd8 loss in astrocytes attenuates neuroinflammation by disrupting astrocyte-microglia interactions and altering metabolic and lipid-related pathways, with these changes reflecting an epigenetic reprogramming of astrocyte function. These findings uncover a novel role of CHD8 in regulating neuroinflammation through astrocytes in the adult brain. Our work suggests a therapeutic potential via targeting CHD8 to mitigate harmful neuroinflammation in neurodegenerative conditions. Currently, we are probing the functions of CHD8 in diverse astrocytic populations and their relevance in neurodegenerative conditions.
Poster #227: Roberto Charles
Title: Internalization and Anti-inflammatory Effects of Dendritic Polyglycerol Sulfate in the Hippocampus
Abstract: Neurological disorders account for billions of dollars of economic impact. In conditions like ischemic stroke, inflammation plays a key role in exacerbating disease progression, yet, addressing this issue remains difficult due to the protective blood-brain barrier. Dendritic polyglycerol sulfate (dPGS) has shown potential both as a nano-delivery compound and as an anti-inflammatory therapeutic. However, its mechanism of action in inflammatory conditions remains understudied, notably, the importance of its highly negative charge on its activity is unclear. We will test the anti-inflammatory effects of dendritic nanostructures with sulfate groups on brain cells (astrocytes, microglia, neurons, and endothelial cells) compared to those with hydroxyl or amino groups with weaker negative charges. Here, we use immunohistochemistry (IHC) to stain for microglia in organotypic hippocampal tissue slices and demonstrate increased internalization of dPGS in microglia and CA1 pyramidal neurons expressing GFP when in bacterial toxin (LPS) induced inflammatory conditions. Using ELISA which measures protein levels, we detected increased levels of alarmin IL-33 which is known to have both neuroprotective and neuroinflammatory effects. Despite their opposing roles, both LPS exposure and dPGS exposure conditions led to the observed increase of IL-33, thus suggesting context-dependent effects of the protein. Our results demonstrate an inflammatory state-dependent activity of dPGS, reinforcing its role as an anti-inflammatory compound. Repeating these experiments with positively charged dendritic polyglycerol amine will elucidate the structure-activity relationship of dPGS and measuring the levels of downstream effectors of IL-33 such as anti-inflammatory cytokine IL-10, will further unravel its anti-inflammatory properties.
Poster #228: Sara Chafik
Title: The association between complement factor C6 and periventricular white matter lesions in multiple sclerosis disease progression
Abstract: The complement system is an essential component of the innate immune response due to its role in assembling the membrane attack complex (MAC), a transmembrane pore that facilitates cell death. Complement proteins have been linked to multiple sclerosis (MS) due to their presence around demyelinating lesions. Preliminary data shows a consistent upregulation of complement C6 in periventricular white matter lesions (PVWML) when compared to other types of lesions. The periventricular area is thought to be especially vulnerable to lesion formation and inflammation as it is in close proximity to the blood-cerebrospinal fluid barrier (BCSFB). C6 is also noteworthy as it is involved in all complement activation pathways and forms part of the MAC. Additionally, mice with experimental MS (experimental autoimmune encephalomyelitis, EAE) that are deficient in the protein are protected from demyelination. Considering our preliminary data and current literature, we hypothesize that C6 is a driving factor of oligodendrocyte death, leading to myelin degradation that promotes inflammation in PVWML, contributing to MS disease progression. This will be tested by analyzing post-mortem brain tissue from MS patients with immunofluorescence microscopy, flow cytometry and RT-qPCR to identify the cellular source of C6. Furthermore, microglia acquired from epileptic patients undergoing brain surgery will be cultured to check C6 expression under normal and inflamed conditions. A better understanding of these mechanisms could open novel therapeutic avenues to slow down disease progression and improve the quality of life of MS patients.
Poster #229: Shobina Premachandran
Title: Investigating the pathological and molecular features of the barrier cells found within the choroid plexus in multiple sclerosis
Abstract: Multiple Sclerosis (MS) is a disease of the central nervous system (CNS), in which autoreactive immune cells enter the brain via a damaged blood brain barrier (BBB) and drive demyelinating lesion formation. Gradients of pathology exist in defined brain regions adjacent to the cerebrospinal fluid (CSF) suggesting that CSF may contain immune cells and proinflammatory factors which promote this damage. However, how these cells and factors gain access to the CSF is ill-defined. The choroid plexus (CP) is responsible for CSF production and regulates solute/cell transport across the blood-cerebrospinal fluid barrier (BCSFB). It has been shown in MS models that immune cells infiltrate the CNS through the CP in prodromal stages of MS, before widespread BBB breakdown. The CP could be the key route of immune cell entry into the CSF where they accumulate and contribute to the CNS damage. We hypothesize that this may be a result of the disruption of barrier and stromal structural cells in the CP of MS patients, contributing to increased barrier permeability. Using ultrastructural analysis through electron microscopy (EM), molecular profiling and immunolabeling, we aim to determine if there are suggestions that the integrity of the CP BSCFB is compromised. To-date, transcriptomic changes coupled with EM observations suggest vasculature dysregulation, a loss of epithelial cohesion, and a reduction in adhesion proteins needed for adherens junction maintenance in the CP MS samples. Uncovering the involvement of the CP in facilitating CSF-mediated damage will be a foundational step for discovering therapeutic interventions to target MS progression.
Poster #230: Shubhendra Mishra
Title: Investigating the role of sildenafil in promoting neuronal plasticity after neonatal HIE: An in-vitro study
Abstract: Introduction: Hypoxic-ischemic encephalopathy (HIE) following birth asphyxia affects 3 in 1000 live births and often leads to severe neurodevelopmental impairments. While therapeutic hypothermia is standard in high-income settings, it fails in 30% of cases and has uncertain efficacy in low-resource environments. Sildenafil, a potential neuroprotective agent, has shown promise in preclinical studies by promoting neuronal survival and network development, but further research is needed. Methods: In this study, primary neurons at day 7 in culture (DIC 7) were subjected to 6 hours of hypoxia (1% O₂) and ischemia (no glucose). A subset received sildenafil (150 nM) for 48 hours. Neuronal morphology was assessed using immunocytochemistry for MAP2 and Tuj1, and analyzed via IMARIS software in three groups: control, hypoxia-ischemia (HI), and HI + sildenafil. Results: At DIC 10, HI significantly reduced dendrite length (42.55±29.62 µm), dendrite number per neuron (0.66±0.80), neurite length (40.80±17.27 µm), and neurite branch number per neuron (1.51±1.04) compared to controls (p < 0.005). Sildenafil treatment significantly restored these measures, with increases in dendrite length (162.69±45.58 µm), dendrite number per neuron (3.50±1.14), neurite length (220.30±80.12 µm), and neurite branch number per neuron (6±2.36) compared to HI (p < 0.005). Conclusion: HI significantly reduced dendrite and neurite markers and structural measures. Sildenafil treatment appeared to protect against deleterious HI effects and preserved dendritic and neurite growth. These findings suggest that sildenafil has a neuroprotective effect against HI.
Poster #231: Skylar Donovan
Title: The Role of Microglial Activation in Dopaminergic Neurodegeneration in a Flp-Dependent Alpha-Synuclein Over-Expression Model of Parkinson’s Disease
Abstract: Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as resting tremors, bradykinesia, and postural instability. These symptoms result from dopamine deficiency in the putamen due to the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). A hallmark of PD pathology is the accumulation of alpha-synuclein (aSyn) aggregates, or Lewy bodies, contributing to neurodegeneration. While the exact mechanisms underlying PD remain unclear, chronic neuroinflammation is increasingly recognized as a key driver of DA neuron loss. Persistent microglial activation, observed in PD patients and animal models, may exacerbate neuronal damage through excessive proliferation, migration, and phagocytosis. To investigate the role of microglial recruitment in PD, we utilized a Flp-dependent aSyn overexpression model in DA neurons. In this model, we observe the loss of TH in the caudate putamen and the progressive loss of DA neurons over 16 weeks. We assessed microglial responses in the substantia nigra, and the putamen compared to mCherry controls. Immunohistochemical staining for IBA1 revealed a significant increase in microglial recruitment in the aSyn-injected SNc and no difference in the striatum. These findings suggest that αSyn accumulation in DA neurons is sufficient to drive an active neuroinflammatory response, potentially contributing to the selective vulnerability of DA neurons in PD.
Poster #232: Teddy Fisher
Title: Molecular Biomimicry and the Synthetic synapse: Engineering a stable synaptogenic extracellular matrix
Abstract: Synapses are specialized sites of asymmetric cell – cell contact that mediate information transfer between neurons. Surprisingly, synaptic differentiation does not require a cellular target. Hemi-synaptic specializations form quickly at sites of neurite adhesion to microspheres coated with a synaptogenic protein or a synthetic cationic polypeptide like poly-lysine. This raises the possibility that functional hemi-synaptic connections could be directed to form onto engineered surfaces, improving information transfer and biocompatibility. However, studies examining the stability of synaptic specializations formed in brain onto poly-lysine coated beads found they degraded within a few weeks after implantation. Here, we demonstrate that microbeads coated with dendritic polyglycerol amine (dPGA), a non-protein macromolecular biomimetic of poly-lysine, promote enhanced synaptogenesis and synapse stability compared to conventional poly-lysine. We show that dPGA-coated beads cluster neurexin, which is sufficient to direct presynaptic terminal formation. Bead curvature was thought to contribute to the formation of hemi-synaptic specializations, preventing the modification of electrodes with flat contact points. To test this, we used cubic micro-hydrogels to show that hemi-synaptic specializations readily form onto flat dPGA coated surfaces. We propose that synthetic synaptogenic extracellular matrices that are resistant to proteolysis could be used to engineer electrodes with enhanced neural-biocompatibility and support bi-directional communication with neurons by directing the formation of stable synaptic specializations.
Poster #233: Veronika Pak
Title: Axes of Whole-Brain Cell-Cell Interactions Underlying Spatial Tissue Vulnerability Across the Neurodegeneration Spectrum
Abstract: Dysregulated communication between neurons, glial cells, and endothelial cells in the brain contributes to inflammation, impaired glutamate metabolism, vascular dysfunction, and neuronal death in neurodegenerative diseases. Understanding how functional interactions among these cell types predispose individuals to different neurodegenerative conditions is crucial for advancing diagnostics and therapeutic treatments. Here, we integrated spatial gene expression data with structural magnetic resonance imaging to generate 1,037 whole-brain maps of ligand-receptor interactions across neurons, astrocytes, microglia, oligodendrocytes, oligodendrocyte precursor cells, and endothelial cells. These maps were created by inferring literature-curated ligand-receptor interaction pairs from microarray gene expression data derived from post-mortem tissues of six healthy human donors, obtained from the Allen Human Brain Atlas. Using partial least squares regression, we identified key axes of cell-cell interactions that explain spatial brain tissue vulnerability across the spectrum of neurodegenerative diseases. Atrophy maps were generated for 13 neurodegenerative conditions, including early- and late-onset Alzheimer’s disease, clinical and pathological subtypes of frontotemporal lobar degeneration, Parkinson’s disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. The first axis, which explained the most tissue damage, involved complex interactions among neurons, astrocytes, and microglia, predominantly capturing atrophy patterns common to subtypes of frontotemporal lobar degeneration and Alzheimer’s disease. All axes were enriched in biological pathways, including the Alzheimer’s disease presenilin pathway, integrin signaling, and cadherin signaling. The identified ligands and receptors, along with their associated cell types and underlying signaling pathways, may serve as potential therapeutic targets and enhance our understanding of neurodegenerative diseases.
HBHL Symposium 