HAI Book 2025 - Flipbook - Page 561
Rissman, Robert
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Detection of TDP-43 from plasma-derived astrocyte extracellular
vesicles for identification of LATE
Robert Rissman
University of Southern California, Neuroscience Translational Research Division, Alzheimer9s Therapeutic
Research Institute, SAN DIEGO, CA, US
1
Background: Limbic predominant age related TDP-43 encephalopathy neuropathological change (LATE-NC) is a
neurodegenerative disease characterized brain disease that mimics Alzheimer9s disease (AD) clinically. LATE-NC
is difficult to diagnose antemortem using clinical information or biomarkers. Recent studies suggest
concentrations of extracellular vesicle (EVs) protein cargo derived from neuronal and glial cells may serve as
useful diagnostic biomarkers for AD and other neurodegenerative diseases. As an initial step, we developed a high
throughout bioassay to detect TDP-43 in plasma derived exosomes for identification of LATE and AD. We will
present data on our current efforts on standardization and validation of the assay as well as specifics of the use of
RT-QuIC/SAA to identify species of TDP-43 that are unique to LATE.
Method: TDP-43 cargo was detected from astrocyte (ADEVs) using antemortem plasma from participants with
autopsy-confirmed diagnoses, including many with LATE (n = 22). =TDP-43 concentrations were compared to a
group of brains from healthy controls, mild cognitively impairment (MCI), and AD dementia (n = 42).
Result: TDP-43 levels from plasma ADEVs were diagnostic for identifying LATE subjects, with or without
comorbid AD pathology. Measurable levels of TDP-43 were detected in EV-depleted plasma and other EV fractions
but these levels were not significantly different amongst the groups. We found no correlation between EV TDP-43
levels with cognition-based variables proximate to death, sex, and APOE carrier status.
Conclusion: TDP-43 in ADEVs may serve as a potential diagnostic tool to rapidly identify subjects with LATE for
screening into clinical trials.
Keywords: LATE, TDP-43, Alzheimer’s disease, autopsy
HAI2025 - 561
