The Aβ₄₂:Aβ₄₀ ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction.

ABSTRACT: The pathophysiological role of Aβ₄₂ oligomers in the onset of Alzheimer's disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of Aβ₄₂ and Aβ₄₀, which is more abundant but less aggregation-prone. This study investigates Aβ₄₂:Aβ₄₀ oligomers in different ratios, examining their adverse effects on endothelial cells, neurons, astroglia, and microglia, as well as in a human blood-brain barrier (BBB) model. Combining label-free Raman microscopy with complementary imaging techniques and biochemical assays, we show the prominent impact of Aβ₄₀ on Aβ₄₂ fibrillation, suggesting an inhibitory effect on aggregation. Mixed oligomers, especially with low proportions of Aβ₄₂

SUBMITTER: Haessler A 

PROVIDER: S-EPMC11664223 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature