Investigation of plasma β‐synuclein levels in different stages of Alzheimer´s disease and relation to amyloid and tau‐PET
Year: 2023
Type: article
Study design: Observational Study
Abstract: Background Synaptic degeneration is a major hallmark of Alzheimer´s disease (AD). Easily accessible biomarkers are needed to study its role in AD pathogenesis and to detect positive effects on synaptic dysfunction in clinical drug trials. β‐Synuclein is an emerging synaptic blood biomarker for AD but changes of β‐synuclein levels in preclinical AD and its associations with amyloid and tau pathology have not yet been studied. Method We measured plasma β‐synuclein levels using immunoprecipitation‐mass spectrometry in the Swedish BioFINDER‐2 study (N = 230) including cognitively unimpaired individuals (CU) with positive Aβ‐PET (CU Aβ+ , i.e. preclinical AD, N = 48) or negative Aβ‐PET (CU Aβ− , N = 61), Aβ‐positive patients with mild cognitive impairment (MCI Aβ+, N = 36) and Aβ‐positive AD dementia (N = 85). Amyloid (A) and tau (T) pathology were assessed by [18F]Flutemetamol and [18 F]RO948 PET, cortical thickness by MRI and cognitive performance using the Mini‐Mental State Examination (MMSE) and modified Preclinical Alzheimer’s Cognitive Composite (mPACC). Result Plasma β‐synuclein levels were increased in CU Aβ+ (p = 0.033) and further increased in MCI Aβ+ (p = 0.007) and AD patients with dementia (p<0.001) compared with CU Aβ−. Furthermore, β‐synuclein levels were higher in AD dementia than in CU Aβ+ (p = 0.002) and MCI Aβ+ (p = 0.037). Stratification according to Aβ‐ and tau‐PET status revealed increased β‐synuclein levels in both A+T− (p = 0.014) and A+T+ (p<0.001) subjects compared with A−T− and further increased in the A+T+ group compared with A+T– group (p<0.001). Plasma β‐synuclein levels significantly correlated with Aβ‐PET SUVR (β = 0.279; p<0.001) and tau‐PET SUVR (β = 0.308; p<0.001) and were associated to temporal cortical thinning (β = ‐0.135; p = 0.044) and worse performance on MMSE (β = ‐0.252; p<0.001) and mPACC (β = ‐0.254; p<0.001). Conclusion Our data indicate that plasma β‐synuclein levels rise early in AD during the preclinical phase, preceding tau pathology, which supports that synaptic degeneration belongs to the very early events in sporadic AD. The results support plasma β‐synuclein as an easily accessible and scalable biomarker that can be used to detect positive effects of novel disease‐modifying therapies on synaptic dysfunction in AD and to further study synaptic degeneration in the pathophysiology of AD.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.074201
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390195160