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

ABSTRACT

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