Sensory, cognitive, and motor functions are impaired in Alzheimer’s disease (AD). This synaptic loss has no association with neurochemical markers in a clinical set-up. Mass spectroscopy confirms beta-synuclein protein as a marker. This study aims to set up an innovative ELISA (enzyme-linked immunosorbent assay) to evaluate beta-synuclein’s predictive potential.

The study assesses beta-synuclein’s predictive ability for AD. A total of 393 patients were selected from 4 specialized centers. The number of AD, Parkinson syndrome (PS), Creutzfeldt-Jakob disease (CJD), amyotrophic lateral sclerosis (ALS) cases were 151, 46, 23, and 29. There were 66 disease control cases, with 60 non-neurodegenerative control patients. 18 patients had behavioral variant frontotemporal dementia (bvFTD). The core AD biomarkers phospho-tau, amyloid-β peptide 1–42, and total tau were compared with the results. The beta-synuclein coexistence with vesicular glutamate transporter 1 (VGLUT1) was determined. The beta-synuclein levels in brain homogenates were also quantified.

The ELISA beta-synuclein levels strongly correlated with antibody free quantitative mass spectrometry data with r=0.92 and p<0.0001. The CSF beta-synuclein levels increased in AD-mild cognitive impairment, AD dementia, and CJD with p<0.0001. But CSF did not increase in bvFTD, Parkinson, or ALS. The VGLUT1 localized beta-synuclein and its expression lowered significantly in AD patient’s brain tissue.

The robust, sensitive ELISA has been successfully established to measure brain-enriched beta-synuclein, localized in glutamatergic synapses. The study confirms beta-synuclein potential as a synaptic degeneration marker in AD, CJD patients with higher CSF levels.