Amyloid, p-tau, neurofilament light, and α-synuclein cerebrospinal fluid biomarkers across Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease.

Mounting evidence suggests overlapping pathology across Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD), yet its extent and clinical implications remain unclear.

Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/40, phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and total α-synuclein were centrally measured using fully-automated Elecsys immunoassays in 347 participants (European Platform for Neurodegenerative Diseases [EPND] cohort) and compared between groups. Associations of amyloid and tau positivity with cognitive and motor function were evaluated.

Compared to controls, amyloid and tau levels were abnormal in DLB, but not in PD. Amyloid and tau positivity in DLB were associated with worse global cognitive outcomes, but not with motor performance. NfL levels were elevated across diseases, and total α-synuclein levels were associated with tau positivity.

AD pathology is observed in DLB, and related to worse cognition, but it is less observed in PD. CSF NfL captures non-disease-specific processes, whereas CSF total α-synuclein likely reflects CSF tau positivity. Results can help patient management in clinical practice and trials.
Mental Health
Care/Management
Policy

Authors

Rizzo Rizzo, Teunissen Teunissen, Zetterberg Zetterberg, Blennow Blennow, Kollmorgen Kollmorgen, Krüger Krüger, Fernandes Fernandes, Aarsland Aarsland, Borejko Borejko, Hu Hu, Chokoshvili Chokoshvili, Vijverberg Vijverberg, Lemstra Lemstra, Tijms Tijms, Petzold Petzold, Brockmann Brockmann, Gasser Gasser, Frisoni Frisoni, Hort Hort, Nedelska Nedelska, Hopøy Hopøy, Fladby Fladby, Jessen Jessen, Düzel Düzel, Spottke Spottke, Höglinger Höglinger, Mutel Mutel, Chevalier Chevalier, Krishnan Krishnan, Visser Visser, Vos Vos,
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