Objective: To determine whether visual hallucinations (VH) in dementia with Lewy bodies (DLB) are associated with α-synuclein oligomers.

Background: It is not known whether VH in DLB are associated with a greater burden of α^‑synuclein pathology compared to those without VH. Evidence suggests that α-synuclein oligomers that represent an early-stage α-synuclein aggregation may be more toxic than Lewy-related pathologies (Lewy bodies and Lewy neurites). We sought to determine if α‑synuclein oligomers were associated with VH in DLB.

Method: Formalin fixed paraffin embedded tissue from 10 prospectively followed patients with Lewy body disease and a clinical diagnosis of DLB were studied. All patients had at least one neuropsychological assessment within 3 years of death. Half of the patients had VH. Lewy-related pathologies and α-synuclein oligomers were visualized with phosphorylated α-synuclein immunohistochemistry and with α-synuclein proximity ligation assay, respectively. The burden of Lewy-related pathologies and α-synuclein oligomers were assessed in primary visual cortex, visual association cortex, inferior temporal cortex, parahippocampal gyrus, amygdala, and nucleus basalis of Meynert blinded to clinical status.

Results: Cases with and without VH did not differ with respect to age at death (VH: 80 ± 7 years vs. No VH: 79 ± 5 years; p = 0.68), Braak neurofibrillary tangle stage (p = 0.81), or Thal amyloid phase (p > 0.99). There was greater α-synuclein oligomer burden in the parahippocampal gyrus in those with compared to those without VH (p = 0.04). In contrast, the burden of Lewy-related pathology did not differ between patients with or without VH (p = 0.15).

Conclusion: DLB with VH had greater α-synuclein oligomers in the parahippocampal gyrus compared to those without VH. The parahippocampal gyrus is a component of the extra‑striate ventral visual pathway that is involved in recognition and identification of objects. Result of this study suggest that accumulation of α-synuclein oligomers in the parahippocampal gyrus may contribute to VH in DLB.

Figure 1 Comparative images of the PHG

Figure 2 Severity of LRP-burden

Figure 3 Severity of αSYN oligomer-burden

Figure 4 Semiquantitative scores

Table 1 Demographic and clinical characteristics

Table 2 Pathological characteristics

Table 3 Group comparisons

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/visual-hallucinations-and-%ce%b1-synuclein-oligomers-in-dementia-with-lewy-bodies-dlb/