Association between visual hallucinations and α-synuclein oligomers in patients with dementia with Lewy bodies

Visual hallucinations (VHs) represent one of the core clinical features of dementia with Lewy bodies (DLB); however, their underlying pathology remains unclear.

We employed proximity ligation assay (PLA) and phosphorylated α-synuclein (αSYN) immunohistochemistry to compare αSYN oligomers and Lewy-related pathology across brain regions along the ventral visual pathway in patients with and without VHs (five patients each).

Greater αSYN oligomer burden in the parahippocampal cortex was observed in patients with VHs compared to those without (p = 0.041), whereas the burden of Lewy-related pathology was similar between groups.

Our findings suggest that αSYN oligomers, rather than conventional Lewy-related pathology, may be more closely associated with VHs in DLB. This provides novel evidence linking αSYN oligomers to a core clinical feature in DLB and suggests potential therapeutic targets for managing VH in these patients.

Visualization of αSYN oligomers by PLA and quantitative neuropathologic analysis. Abundant αSYN oligomers in parahippocampal cortex of DLB with VHs. First human brain study linking αSYN oligomers to VHs. Potential oligomer-targeted therapy for managing VH in DLB.