Stage-Dependent β-Synuclein Links MRI and Cognitive Decline in Alzheimer's Disease
Annals of Clinical and Translational Neurology, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/acn3.70494
- Dergi Adı: Annals of Clinical and Translational Neurology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: Alzheimer's disease, beta synuclein, neurodegeneration, neuroimaging, synaptic biomarker
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet
Özet
Objective: Synaptic degeneration drives cognitive decline in Alzheimer's disease (AD), but synaptic biomarkers are scarce. Brain-enriched β-synuclein emerged as a synaptic damage marker. We investigated its diagnostic, prognostic, and structural correlates across the AD continuum. Methods: In a tertiary-center cohort (n = 306), CSF β-synuclein was measured. Cognitively unimpaired (CU), AD-MCI, AD dementia (ADD), and non-AD (FTD, PD, DLB, others) groups were included. ANCOVA compared groups (age/sex adjusted); ROC assessed diagnostic performance. Multivariable regression examined 2-year MMSE decline associations. Voxel-wise interaction models evaluated β-synuclein–gray matter volume (GMV) relationships. Results: CSF β-synuclein differed across groups (p < 0.001), with highest levels observed in AD-MCI and lower levels in ADD. AD-MCI levels exceeded CU/ADD. AD-MCI versus CU AUC was 0.874. Baseline β-synuclein predicted greater MMSE decline in AD-MCI (β = 0.72, p < 0.001) and ADD (β = 0.47, p = 0.017). Voxel-wise analyses revealed stage-dependent β-synuclein–GMV reversals in precentral and temporoparietal regions. Conclusion: CSF β-synuclein shows a stage-dependent pattern across the AD continuum, predicts cognitive decline, and dynamic structural coupling. It supports β-synuclein as a relevant synaptic biomarker in AD.