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Familial Alzheimer Mutations in Presenilin-1 Decrease APP Substrate Proteolysis by γ-Secretase via Stable Enzyme-Substrate Complex Formation

2025-05-19

Abstract excerpt

Familial Alzheimer’s disease (FAD) is caused by dominant missense mutations in am-yloid precursor protein (APP) and presenilin-1 (PSEN1), the catalytic component of γ-secretase, that generates amyloid β-peptides (Aβ) from the APP C-terminal fragment C99. While most FAD mutations increase the ratio of aggregation-prone Aβ42 relative to Aβ40, consistent with the amyloid hypothesis of Alzheimer pathogenesis, some mut...

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Literature Corpus work: dd38cb5e-d6fd-541b-a042-f5014d69e05a
DOI: 10.20944/preprints202505.1338.v1

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