{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:13:12Z","timestamp":1793679192960,"version":"4.5.1"},"reference-count":40,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2020,11,24]]},"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Synaptic loss plays a major role in Alzheimer\u2019s disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was established as a candidate marker. We now aimed to set up a novel ELISA for beta-synuclein for evaluation of its potential as a diagnostic and predictive marker for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed in total 393 patients from four specialised centres. The diagnostic groups comprised: AD (n=151), behavioural variant frontotemporal dementia (bvFTD, n=18), Parkinson syndrome (n=46), Creutzfeldt-Jakob disease (CJD, n=23), amyotrophic lateral sclerosis (ALS, n=29), disease control (n=66) and 60 non-neurodegenerative control patients. Results were compared with core AD biomarkers (total tau, phospho-tau and amyloid-\u03b2 peptide 1\u201342). Additionally, coexistence of beta-synuclein with vesicular glutamate transporter 1 (VGLUT1) was determined and beta-synuclein levels were quantified in brain homogenates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Beta-synuclein levels quantified with the newly established ELISA correlated strongly with antibody-free quantitative mass spectrometry data (r=0.92 (95% CI: 0.89 to 0.94), p&lt;0.0001). Cerebrospinal fluid (CSF) beta-synuclein levels were increased in AD-mild cognitive impairment (p&lt;0.0001), AD dementia (p&lt;0.0001) and CJD (p&lt;0.0001), but not in bvFTD, Parkinson syndrome or ALS. Furthermore, beta-synuclein was localised in VGLUT1-positive glutamatergic synapses, and its expression was significantly reduced in brain tissue from patients with AD (p&lt;0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We successfully established a sensitive and robust ELISA for the measurement of brain-enriched beta-synuclein, which we could show is localised in glutamatergic synapses. We confirmed previous, mass spectrometry-based observations of increased beta-synuclein levels in CSF of patients with AD and CJD supporting its potential use as a marker of synaptic degeneration.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2020-324306","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T18:31:19Z","timestamp":1609353079000},"page":"349-356","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer\u2019s 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