Confluence of α-Synuclein, Tau, and β-Amyloid Pathologies in Dementia With Lewy Bodies

Dementia with Lewy bodies (DLB) is pathologically characterized by alpha-synuclein aggregates in the brain. Most patients with DLB also show cerebral Alzheimer disease-type pathology (i.e. beta-amyloid plaques and hyperphosphorylated tau deposits). It is unclear whether this overlap is coincidental or driven by specific regional or cellular interactions. The aims of this study were to investigate the regional convergence of alpha-synuclein, tau, and beta-amyloid and to identify patterns of cellular co-occurrence of tau and alpha-synuclein in DLB. The study group consisted of 22 patients who met clinical and neuropathologic criteria for DLB. Protein aggregates were assessed semiquantitatively in 17 brain areas. APOE and MAPT genotypes were determined. Cellular co-occurrence of tau and alpha-synuclein was evaluated by double immunofluorescence. We found that total beta-amyloid pathology scores correlated positively with total alpha-synuclein pathology scores (rho = 0.692, p = 0.001). The factors that correlated best with the amount of alpha-synuclein pathology were the severity of beta-amyloid pathology and presence of the MAPT H1 haplotype. Tau and alpha-synuclein frequently colocalized in limbic areas, but no correlation between total pathology scores was observed. This study confirms and extends the role of beta-amyloid deposition and the MAPT H1 haplotype as contributing factors in DLB pathogenesis and demonstrates the confluence of multiple agents in neurodegenerative diseases.