Neurodegeneration and Cell Death*
Date: October 18, 2026
Time: 3:30 pm to 5:00 pm
Room: Coral 5
Track: Cross-Cutting Special Interest Group (SIG)
Session Description
This session will explore current advances in the basic and translational science of neurodegeneration and cell death. Faculty will review emerging insights into the molecular and cellular mechanisms that drive neurodegenerative processes and highlight how these discoveries are informing the development of novel therapeutic strategies.
The session will also examine the critical interface between basic and translational research, emphasizing the importance of effective collaboration among academic investigators, clinicians, and industry partners. By bridging these domains, the session aims to highlight pathways for accelerating the translation of mechanistic discoveries into meaningful clinical applications.
Learning Objectives
At the conclusion of this session, attendees will be able to:
- Summarize recent advances in basic research on the mechanisms of neurodegeneration.
- Evaluate translational research approaches that link mechanistic insights to therapeutic development.
- Analyze strategies to enhance collaboration and communication among basic scientists, clinicians, and industry partners.
Speakers
Can Modulating Sleep Mitigate Neurodegeneration?
Description
Tauopathies, including Alzheimer’s disease and frontotemporal dementia, represent a major and growing public health challenge, highlighting the need to identify early, modifiable disease processes that can delay or prevent neurodegeneration. Sleep dysfunction is a common and often early feature across neurodegenerative diseases raising the possibility that targeting disrupted sleep may provide a therapeutic opportunity before substantial neuronal loss occurs.
This presentation will address a central question: Can modulation of sleep and wakefulness effectively counteract tau-mediated neurodegeneration? Participants will examine evidence from animal models and humans demonstrating a reciprocal relationship between sleep/wake disruption and tau pathology. The presentation will explore how manipulating sleep influences molecular and pathological biomarkers of neurodegeneration and whether the mechanisms through which sleep is altered are as important as the amount of sleep itself.
Particular emphasis will be placed on sleep/wake-regulating pathways, including orexin and GABAergic signaling, and their differential effects on tau pathology, neuroinflammation, and neurodegeneration. Attendees will gain an understanding of the molecular mechanisms linking sleep-regulatory systems to tau-mediated neurodegeneration and the potential for targeting specific sleep/wake pathways as therapeutic strategies for tauopathies.
Mechanisms of Neuronal Toxicity in C9ORF72-associated ALS and FTD
Description
Hexanucleotide repeat expansions in C9ORF72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although both toxic repeat RNAs and dipeptide repeat proteins generated through repeat-associated non-AUG (RAN) translation have been implicated in disease pathogenesis, their relative contributions to neurodegeneration have remained a critical unanswered question.
This presentation will examine the molecular mechanisms underlying neuronal toxicity in C9ORF72-associated ALS and FTD, highlighting a novel genetic approach that selectively inhibits RAN translation without altering repeat RNA expression. Participants will review findings from mouse models and patient-derived induced pluripotent stem cell (iPSC) neurons demonstrating that suppression of dipeptide repeat protein production significantly improves behavioral outcomes and neuropathological features despite the continued presence of toxic repeat RNA. Topics will include the implications of these findings for understanding disease pathogenesis and how targeting RAN translation and dipeptide repeat proteins may inform the development of future disease-modifying therapies.
Attendees will leave with a greater understanding of the pathogenic mechanisms underlying C9ORF72-associated ALS and FTD and practical insights into emerging therapeutic strategies aimed at preventing neurodegeneration through selective targeting of dipeptide repeat protein production.
Genetically Determined Resilience to Alzheimer's Disease Is Independent of Genetic Risk and Gated by Cardiovascular Comorbidity
Description
While much Alzheimer’s disease research has focused on genetic risk factors, increasing attention is being given to the biological mechanisms that promote resilience to neurodegeneration. Understanding why some individuals preserve brain structure and cognition despite substantial amyloid burden may reveal new strategies for disease prevention and therapeutic intervention.
This presentation will explore the concept of genetically determined resilience to Alzheimer’s disease and its relationship to cardiovascular health. Participants will examine evidence demonstrating that resilience is a distinct inherited axis rather than the absence of genetic risk, review the development and application of the Polygenic Resilience Score (PReS) as a measure of active brain protection, and discuss findings across 27,961 individuals in three independent cohorts, including an estimated 5.9 additional dementia free years in the discovery cohort. Topics will also include how cardiovascular state and treatment with statins and antihypertensives gate the protective effect of genetic resilience, and the implications for precision medicine and dementia prevention.
Attendees will leave with a greater understanding of the emerging science of genetic resilience in Alzheimer’s disease and practical insights into how resilience informed approaches and cardiovascular risk modification may shape future strategies for predicting, preventing, and delaying dementia.
Proteomic Age Acceleration in Multiple Sclerosis Precedes Symptom Onset and Associates with Disease Severity
Description
Multiple sclerosis (MS) is a complex, progressive neurological disease in which biological changes may occur well before the onset of clinical symptoms. Emerging research using proteomic measures of biological aging offers new opportunities to identify early disease-related changes and better understand the mechanisms underlying disease progression and severity.
This presentation will examine multi-organ proteomic aging in MS and its relationship to disease onset and clinical severity. Participants will explore evidence that proteomic age acceleration may precede the development of MS symptoms and examine how these measures are associated with disease burden and severity. The session will also discuss the potential of proteomic approaches to improve understanding of disease biology and identify biomarkers that may support earlier detection, risk stratification, and monitoring of MS.
Attendees will leave with a greater understanding of the relationship between biological aging and MS and emerging insights into how proteomic measures may help identify disease-related changes before symptom onset and better characterize disease severity.
Multiplex Proteomics of Lewy Body Dementia Reveals Cerebrospinal Fluid Biomarkers of Clinical and Neuropathological Heterogeneity
Description
Advances in biofluid proteomics are expanding the ability to characterize the clinical and neuropathological heterogeneity of Lewy body dementia (LBD), including Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB). Emerging protein biomarkers provide an opportunity to better define molecular changes associated with cognitive impairment and progression while distinguishing the contributions of α-synuclein, amyloid-β, and other co-occurring pathologies.
This presentation will review recent advances in cerebrospinal fluid proteomics in LBD, highlighting protein signatures associated with clinical diagnosis, cognitive progression, and underlying neuropathology. Participants will explore how α-synuclein and amyloid-β pathologies influence biofluid protein profiles, including synaptic biomarkers that show distinct or opposing relationships with these pathologies. The presentation will also discuss how neuropathological co-pathology can complicate biomarker interpretation and how large, well-characterized cohorts can help identify and validate disease-relevant protein signatures.
Attendees will leave with a greater understanding of emerging biofluid biomarkers of LBD heterogeneity and practical insights into how proteomic signatures may complement established biomarkers, improve the interpretation of mixed pathology, and ultimately support more precise molecular characterization and clinical assessment of patients with Lewy body disease.
