Lysosomal and Synaptic Dysfunction Markers in Longitudinal Cerebrospinal Fluid of De Novo Parkinson’s Disease

Michael Bartl,Johanna Nilsson,Mohammed Dakna,Sandrina Weber,Sebastian Schade,Mary Xylaki,Barbara Fernandes Gomes,Marielle Ernst,Maria-Lucia Muntean,Friederike Sixel-Doering,Claudia Trenkwalder,Henrik Zetterberg,Ann Brinkmalm,Brit Mollenhauer

Journal Of Neurochemistry（2024）SCI 2区SCI 3区

Univ Med Ctr Goettingen | Univ Gothenburg | Paracelsus Elena Klin | Sahlgrens Univ Hosp

Cited 0|Views33

Abstract

Lysosomal and synaptic dysfunctions are hallmarks in neurodegeneration and potentially relevant as biomarkers, but data on early Parkinson’s disease (PD) is lacking. We performed targeted mass spectrometry with an established protein panel, assessing autophagy and synaptic function in cerebrospinal fluid (CSF) of drug-naïve de novo PD, and sex-/age-matched healthy controls (HC) cross-sectionally (88 PD, 46 HC) and longitudinally (104 PD, 58 HC) over 10 years. Multiple markers of autophagy, synaptic plasticity, and secretory pathways were reduced in PD. We added samples from prodromal subjects (9 cross-sectional, 12 longitudinal) with isolated REM sleep behavior disorder, revealing secretogranin-2 already decreased compared to controls. Machine learning identified neuronal pentraxin receptor and neurosecretory protein VGF as most relevant for discriminating between groups. CSF levels of LAMP2, neuronal pentraxins, and syntaxins in PD correlated with clinical progression, showing predictive potential for motor- and non-motor symptoms as a valid basis for future drug trials.

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