PT  - JOURNAL ARTICLE
AU  - Marc D. Tambini
AU  - Luciano D’Adamio
TI  - Loss of CDC50A function drives Aβ/p3 production via increased β/α-secretase processing of APP
AID  - 10.1101/2020.11.12.379636
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.12.379636
4099  - http://biorxiv.org/content/early/2020/11/12/2020.11.12.379636.short
4100  - http://biorxiv.org/content/early/2020/11/12/2020.11.12.379636.full
AB  - The Amyloid Precursor Protein (APP) undergoes extensive proteolytic processing to produce several biologically active metabolites which affect Alzheimer’s disease (AD) pathogenesis. Sequential cleavage of APP by β- and γ-secretases results in Aβ, while cleavage by α- and γ-secretases produces the smaller p3 peptide. Here we report that in cells in which the P4-ATPase flippase subunit CDC50A has been knocked out, large increases in the products of β- and α-secretase cleavage of APP (sAPPβ/βCTF and sAPPα/αCTF, respectively) and the downstream metabolites Aβ and p3 are seen. These data indicate that APP cleavage by β/α-secretase are increased and suggest that phospholipid asymmetry plays an important role in APP metabolism and Aβ production.Competing Interest StatementThe authors have declared no competing interest.