Beta-synuclein levels in CSF may spot Alzheimer’s disease early

Enriched beta-synuclein levels in cerebrospinal fluid (CSF) may be used as a marker of synaptic degeneration in Alzheimer’s disease (AD), a study has found.

A total of 393 patients underwent a novel ELISA assay for beta-synuclein to evaluate its potential as a diagnostic and predictive marker for AD. Of the patients, 151 had AD, 18 had behavioural variant frontotemporal dementia (bvFTD), 46 had Parkinson syndrome, 23 had Creutzfeldt-Jakob disease (CJD), and 29 had amyotrophic lateral sclerosis (ALS, n=29). The remaining patients served as disease control (n=66) and non-neurodegenerative control (n=60).

Assay results were examined against core AD biomarkers (ie, total tau, phospho-tau, and amyloid-β peptide 1–42). The coexistence of beta-synuclein with vesicular glutamate transporter 1 (VGLUT1) was also determined, and beta-synuclein levels were quantified in brain homogenates.

Beta-synuclein levels measured using the newly established ELISA showed a strong correlation with antibody-free quantitative mass spectrometry data (p<0.0001). Specifically, CSF beta-synuclein levels were elevated in AD-mild cognitive impairment (p<0.0001), AD dementia (p<0.0001), and CJD (p<0.0001), but not in bvFTD, Parkinson syndrome, or ALS.

Moreover, beta-synuclein concentration was found in VGLUT1-positive glutamatergic synapses, and its expression was significantly diminished in brain tissue from patients with AD (p<0.01).

Synaptic loss plays a crucial role in AD, and the present data demonstrate a sensitive and robust ELISA assay for the measurement of brain-enriched beta-synuclein, which is localized in glutamatergic synapses. Mass spectrometry-based observations of elevated beta-synuclein levels in CSF may be therefore used as a marker of synaptic degeneration.