Blood β-synuclein is related to amyloid PET positivity in memory clinic patients

Abstract

Introduction: β-synuclein is an emerging blood biomarker to study synaptic degeneration in Alzheimer´s disease (AD), but its relation to amyloid-β (Αβ) pathology is unclear. Methods: We investigated the association of plasma β-synuclein levels with [18F]flutemetamol positron emission tomography (PET) in patients with AD dementia (n = 51), mild cognitive impairment (MCI–Aβ+ n = 18, MCI– Aβ– n = 30), non-AD dementias (n = 22), and non-demented controls (n = 5). Results: Plasma β-synuclein levels were higher in Aβ+ (AD dementia, MCI–Aβ+) than in Aβ– subjects (non-AD dementias, MCI–Aβ−) with good discrimination of Aβ+ from Aβ– subjects and prediction of Aβ status in MCI individuals. A positive correlation between plasma β-synuclein and Aβ PET was observed in multiple cortical regions across all lobes. Discussion: Plasma β-synuclein demonstrated discriminative properties for Aβ PET positive and negative subjects. Our data underline that β-synuclein is not a direct marker of Aβ pathology and suggest different longitudinal dynamics of synaptic degeneration versus amyloid deposition across the AD continuum. Highlights: Blood and CSF β-synuclein levels are higher in Aβ+ than in Aβ− subjects. Blood β-synuclein level correlates with amyloid PET positivity in multiple regions. Blood β-synuclein predicts Aβ status in MCI individuals.