Cerebrospinal fluid β-synuclein as a synaptic biomarker for preclinical Alzheimer's disease

J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):83-86. doi: 10.1136/jnnp-2022-329124. Epub 2022 Aug 9.

Abstract

Introduction: β-synuclein (β-syn) is a presynaptic protein, whose cerebrospinal fluid (CSF) levels are increased in patients with Alzheimer's diseases (AD) showing mild cognitive impairment (MCI) and dementia (dem). Here, we aimed to investigate CSF β-syn in subjects at different AD stages, including preclinical AD (pre-AD), and to compare its behaviour with another synaptic biomarker, α-synuclein (α-syn), and two biomarkers of neuro-axonal damage, namely neurofilament light chain protein (NfL) and total tau protein (t-tau).

Methods: We measured β-syn, α-syn, t-tau and NfL in CSF of 75 patients with AD (pre-AD n=17, MCI-AD n=28, dem-AD n=30) and 35 controls (subjective memory complaints, SMC-Ctrl n=13, non-degenerative neurological disorders, Dis-Ctrl n=22).

Results: CSF β-syn, α-syn, t-tau were significantly elevated in pre-AD patients compared with controls (p<0.0001, p=0.02 and p=0.0001, respectively), while NfL only increased in dem-AD (p=0.001). Pre-AD cases showed lower t-tau concentrations than MCI-AD (p=0.04) and dem-AD (p=0.01). CSF β-syn had the best diagnostic performance for the discrimination of pre-AD subjects from all controls (area under the curve, AUC=0.97) and from SMC-Ctrl subjects (AUC=0.99).

Discussion: CSF β-syn increases in the whole AD continuum since the preclinical stage and represents a promising biomarker of synaptic damage in AD.

Keywords: CSF; alzheimer's disease; dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / psychology
  • Humans
  • beta-Synuclein
  • tau Proteins / cerebrospinal fluid

Substances

  • beta-Synuclein
  • tau Proteins
  • Biomarkers
  • Amyloid beta-Peptides