Multiplex plasma profiling of synaptic biomarkers in Alzheimer’s disease using NULISA: early alterations, APOE genotype effects, and pTau217 associations
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INTRODUCTION
Synaptic markers are altered in the CSF of Alzheimer’s disease (AD) patients, but their quantification in plasma remains challenging. We evaluated plasma synaptic markers in MCI and mild AD using the nucleic acid–linked immuno-sandwich assay (NULISA) and their correlation with APOE genotype.
METHODS
272 participants (154 CSF-confirmed AD, 118 controls) underwent plasma assessment with the NULISA CNS panel. A subset ( n =48) also had CSF measurements. Analyses were adjusted for age, sex, comorbidity, and renal function.
RESULTS
NULISA revealed plasma alterations in NPTX2, NPTXR, SNAP-25, and VSNL1 in AD, with SNAP-25 and NPTXR already altered at MCI stage. APOE ε4/ε4 carriers showed higher plasma SNAP-25. Plasma SNAP-25 and NPTXR correlated positively with pTau217. No plasma-CSF concordance was observed.
DISCUSSION
NULISA identifies plasma synaptic biomarker alterations in early AD, with APOEε4 influencing SNAP-25 levels. Associations with pTau217 suggest a link between synaptic damage and tau phosphorylation. Longitudinal studies are warranted.
