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ePoster
THE ALZHEIMER’S PROTECTIVE A2T MUTATION ALTERS AΒ42 AGGREGATION PROPERTIES AND INDUCES CHANGES IN HUMAN NEURAL STEM CELL DIFFERENTIATION
Cristina Soriano-Amadorand 8 co-authors
Instituto de Salud Carlos III
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS06-09PM-145
Presentation
Date TBA
Board: PS06-09PM-145
Event Information
Poster Board
PS06-09PM-145
Poster
View posterAbstract
The accumulation of Amyloid-β (Aβ42) oligomers and plaques is a hallmark of Alzheimer’s Disease (AD). The A2T mutation in the APP gene confers a strong protective effect against AD. While the impact of Aβ42 on mature neurons is well documented, the influence of the protective A2T variant on the regenerative potential of human Neural Stem Cells (hNSCs) remains less understood. This study investigates how Aβ42, comparing Wild-Type (WT) and the A2T variant, differentially modulates hNSC biology, likely due to distinct aggregation behaviors.
Methods: hNS1 cells undergoing differentiation were exposed to varying concentrations of synthetic WT or A2T Aβ42 peptides. Effects on cell viability, proliferation, and lineage specification were assessed via immunocytochemistry and qRT-PCR targeting neuronal (β-III-tubulin) and glial (GFAP) markers. We characterized the aggregation profile of WT and A2T Aβ42 peptides using Transmission Electron Microscopy (TEM).
Results: WT Aβ42 exhibited high toxicity and induced variations in hNSC differentiation. The A2T variant showed reduced toxicity. A2T treatment promoted dose-dependent changes in β-III-tubulin expression. TEM analysis indicated that the A2T mutation modifies the peptide’s self-assembly process compared to WT Aβ42, resulting in structurally distinct fibrillar aggregates.
Conclusion: While WT Aβ42 exerts significant toxicity, the A2T variant does not. This indicates that the protective mechanism of A2T may involve the formation of less toxic assemblies that actively support neuronal differentiation, offering new insights into therapeutic strategies based on Aβ structural modulation. Our findings suggest a link between the modified aggregation properties of the A2T variant and the preservation of hNSC function.
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