Higher plasma β‐synuclein indicates early synaptic degeneration in Alzheimer's disease
Patrick Oeckl, Shorena Janelidze, Steffen Halbgebauer, Erik Stomrud, Sebastian Palmqvist, Markus Otto, Oskar Hansson
Abstract
Abstract INTRODUCTION β‐Synuclein is an emerging synaptic blood biomarker for Alzheimer's disease (AD) but differences in β‐synuclein levels in preclinical AD and its association with amyloid and tau pathology have not yet been studied. METHODS We measured plasma β‐synuclein levels in cognitively unimpaired individuals with positive Aβ‐PET (i.e., preclinical AD, N = 48) or negative Aβ‐PET ( N = 61), Aβ‐positive patients with mild cognitive impairment (MCI, N = 36), and Aβ‐positive AD dementia ( N = 85). Amyloid (A) and tau (T) pathology were assessed by [ 18 F]flutemetamol and [ 18 F]RO948 PET. RESULTS Plasma β‐synuclein levels were higher in preclinical AD and even higher in MCI and AD dementia. Stratification according to amyloid/tau pathology revealed higher β‐synuclein in A + T − and A + T + subjects compared with A − T − . Plasma β‐synuclein levels were related to tau and Aβ pathology and associated with temporal cortical thinning and cognitive impairment. DISCUSSION Our data indicate that plasma β‐synuclein might track synaptic dysfunction, even during the preclinical stages of AD. HIGHLIGHTS Plasma β‐synuclein is already higher in preclinical AD. Plasma β‐synuclein is higher in MCI and AD dementia than in preclinical AD. Aβ‐ and tau‐PET SUVRs are associated with plasma β‐synuclein levels. Plasma β‐synuclein is already higher in tau‐PET negative subjects. Plasma β‐synuclein is related to temporal cortical atrophy and cognitive impairment.