Objective: We examined whether the plasma biomarkers pTau181, pTau217, GFAP, NfL, and Aβ42/40 are associated with cognitive, functional, and motor outcomes in individuals with neuronal αSyn disease.

Background: Plasma biomarkers have been studied in clinically diagnosed Parkinson´s disease (PD) and dementia with Lewy body (DLB) patients, but not individuals with known α-synuclein (αSyn) status, also referred to as neuronal αSyn disease. As accessible and non-invasive tools, plasma biomarkers can assess relative effects of multiple neuropathological processes on cognition, motor function, and daily functioning in neuronal αSyn disease.

Method: To determine whether associations between plasma biomarkers and clinical outcomes differ based on underlying pathology, participants were grouped by positive and negative αSyn (αSyn+/-) and amyloid-β (Aβ+/-) status determined by cerebrospinal fluid (CSF) assay. CSF αSyn status was measured using SAAmplify and CSF Aβ42/Aβ40 status with the Lumipulse G platform. Plasma pTau181 and Aβ42/40 were measured using the Lumipulse G platform, pTau217 with the ALZpath pTau217 assay, and GFAP and NfL with the Neurology 2-plex E kit (Quanterix). Cross-sectional linear regression models adjusted for age, sex, and education analyzed whether each biomarker predicted global cognition (MoCA), daily functioning (CDR sum of boxes), and motor symptoms (UPDRS Part III).

Results: We studied 167 Stanford research participants (mean [SD] age = 69 [7.6]) across 4 groups: 56 αSyn-/Aβ-, 44 αSyn-/Aβ+, 39 αSyn+/Aβ-, and 28 αSyn+/Aβ+. Preliminary results showed higher pTau181, pTau217, GFAP and NfL levels were associated with worse MoCA and CDR-SOB scores in αSyn-/Aβ+ and αSyn+/Aβ+ groups (Fig. 1 and 2). Higher NfL was associated with worse MoCA scores in the αSyn+/Aβ-group (Fig. 1). Only NfL was related to motor impairment, with higher levels associated with worse UPDRS Part III scores in the αSyn+/Aβ+ group (Fig. 3). There were no associations between plasma Aβ42/40 and clinical outcomes.

Conclusion: Plasma biomarkers for detecting amyloidosis (pTau18, pTau217), astrocytic activation (GFAP), and neurodegeneration (NfL) predict cognitive and functional outcomes cross-sectionally in individuals with neuronal αSyn disease and Aβ co-pathology. Findings highlight potential use of plasma biomarkers for screening and stratification in clinical trials for α-synucleinopathies such PD and DLB.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-biomarkers-predict-clinical-outcomes-in-individuals-with-neuronal-%ce%b1-synuclein-disease-and-amyloid-%ce%b2-co-pathology/