Aβ42 biomarker linked to insula, striatum, thalamus and claustrum in dementia with Lewy bodies

The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau₁₈₁) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort. Within the cohort, 65 DLB patients, 18 AD patients, 24 AD + DLB patients and 16 neurological control subjects (NC) were clinically diagnosed. Correlation analyses were performed between cerebrospinal fluid biomarker levels and gray matter volumes using a voxel-based morphometry approach. A mediation analysis was performed to explore the role of gray matter volumes in the relationship between Aβ42 levels and clinical severity (MMSE scores). We observed a significant positive correlation between gray matter volumes and cerebrospinal fluid Aβ42 levels in the insula, the striatal regions, the right thalamus, and the claustrum in DLB patients (p_FDR < 0.05). Mediation analysis revealed that gray matter volumes significantly mediated the relationship between Aβ42 levels and MMSE scores in DLB patients. We found no significant correlation with gray matter volumes for α-synuclein, p-Tau₁₈₁ or t-Tau in DLB patients (p_FDR < 0.05). We found no significant correlations in the AD, AD + DLB and NC groups for any of the biomarkers (p_FDR < 0.05). The specific correlation between a reduced cerebrospinal fluid Aβ42 level and lower gray matter volumes in insula, striatum, thalamus, and claustrum in DLB patients suggests a prominent role for amyloidopathy in promoting brain atrophy in key regions of the disease.