Introduction: The in vivo detection of mixed Alzheimer's disease (AD) and α-synuclein (αSyn) pathology is important for clinical management and prognostic stratification. We investigated the contribution of αSyn pathology, detected by cerebrospinal fluid (CSF) seed amplification assay (αSyn SAA), on [18F]-fluorodeoxyglucose positron emission tomography (FDG PET) pattern in subjects with amnestic mild cognitive impairment (aMCI).
Methods: We included 562 aMCI participants and 204 cognitively normal controls (CN) with available αSyn SAA and cerebral metabolic rate for glucose utilization (rCMRgl) data.
Results: 24% of aMCI cases were positive (+) for CSF αSyn SAA. Compared to CN, both αSyn+ and negative (-) aMCI participants showed reductions in rCMRgl within AD typical regions. αSyn+ aMCI had lower rCMRgl within AD and dementia with Lewy bodies (DLB) typical regions compared to αSyn- aMCI, even after stratification according to the CSF AT(N) system.
Discussion: αSyn pathology contributes to a distinct FDG PET pattern in aMCI.
Highlights: αSyn pathology can be detected in vivo by CSF αSyn SAA. We investigated the FDG PET pattern in aMCI patients with CSF αSyn SAA positivity. αSyn+ aMCI showed a marked brain hypometabolism in AD and DLB typical regions.
Keywords: Alzheimer's disease; Lewy body disease; PET; biomarker.
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.