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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)