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Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss?

Journal article
Authors Annika Öhrfelt Olsson
Pierre Grognet
Niels Andreasen
Anders Wallin
Eugeen Vanmechelen
Kaj Blennow
Henrik Zetterberg
Published in Neuroscience letters
Volume 450
Issue 3
Pages 332-5
ISSN 0304-3940
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 332-5
Language en
Keywords Aged, Alzheimer Disease, cerebrospinal fluid, diagnosis, physiopathology, Biological Markers, analysis, cerebrospinal fluid, Brain, metabolism, pathology, physiopathology, Down-Regulation, physiology, Enzyme-Linked Immunosorbent Assay, methods, Female, Humans, Lewy Body Disease, cerebrospinal fluid, diagnosis, physiopathology, Male, Middle Aged, Neurodegenerative Diseases, cerebrospinal fluid, diagnosis, physiopathology, Neuropsychological Tests, Parkinson Disease, cerebrospinal fluid, diagnosis, physiopathology, Predictive Value of Tests, Synapses, metabolism, pathology, alpha-Synuclein, analysis, cerebrospinal fluid
Subject categories Psychiatry


The association of alpha-synuclein (alpha-syn) neuropathology with Parkinson's disease (PD) and several related disorders has led to an intense research effort to develop cerebrospinal fluid (CSF)- or blood-based alpha-syn biomarkers for these types of diseases. Recent studies show that alpha-syn is present in CSF and possible to measure using enzyme-linked immunosorbent assay (ELISA). Here, we describe a novel ELISA that allows for quantification of alpha-syn in CSF down to 50pg/mL. The diagnostic value of the test was assessed using CSF samples from 66 Alzheimer's disease (AD) patients, 15PD patients, 15 patients with dementia with Lewy bodies (DLB) and 55 cognitively normal controls. PD and DLB patients and controls displayed similar CSF alpha-syn levels. AD patients had significantly lower alpha-syn levels than controls (median [inter-quartile range] 296 [234-372] and 395 [298-452], respectively, p<0.001). Moreover, AD patients with mini-mental state examination (MMSE) scores below 20 had significantly lower alpha-syn than AD patients with MMSE scores of 20 or higher (p=0.02). There was also a tendency towards a negative correlation between alpha-syn levels and disease duration in the AD group (r=-0.247, p=0.06). Altogether, our results speak against CSF alpha-syn as a reliable biomarker for PD and DLB. The lower alpha-syn levels in AD, as well as the association of alpha-syn reduction with AD severity, approximated by MMSE, suggests that it may be a general marker of synapse loss, a hypothesis that warrants further investigation.

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