Multiplex plasma profiling of synaptic biomarkers in Alzheimer's disease using NULISA: early alterations, APOE genotype effects, and pTau217 associations
Martinuzzo, C.; Pilotto, A.; Tolassi, C.; Sauer, M.; Benedet, A. L.; Rondina, A.; Galli, A.; Merati, T.; Trasciatti, C.; Girotto, I.; Di Molfetta, G.; Pola, I.; Tan, K.; Traichel, W.; Caratozzolo, S.; Pelucchi, S. C.; Marcello, E.; Gardoni, F.; Di Luca, M.; Zetterberg, H.; Ashton, N. J.; Padovani, A.
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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 immunosandwich 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, SNAP25, and VSNL1 in AD, with SNAP25 and NPTXR already altered at MCI stage. APOE e4/e4 carriers showed higher plasma SNAP25. Plasma SNAP25 and NPTXR correlated positively with pTau217. No plasma/CSF concordance was observed. DISCUSSION: NULISA identifies plasma synaptic biomarker alterations in early AD, with APOE e4 influencing SNAP25 levels. Associations with pTau217 suggest a link between synaptic damage and tau phosphorylation. Longitudinal studies are warranted.
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