biostudies-literatureUnknown20(9)Jeon SAlzheimer's disease is the most common form of dementia, and multiple lines of evidence support the relevance of Aβ deposition and amyloid plaque accumulation in the neurotoxicity and cognitive decline in AD. Rare mutations in angiotensin-converting-enzyme-1 have been highly associated with late onset AD patients; however, the mechanism for ACE1 mutation in AD pathogenesis is unknown. While numerous studies have shown that ACE1 indeed catabolizes Aβ, majority of these studies were performed in vitro, and conflicting results have been reported in clinical and in vivo systems. Therefore, we further investigated this in vivo by generating and examining a novel mouse model. Specifically, we analyzed 6-month-old 5XFAD mice with ACE1 knockdown restricted to excitatory neurons, achieved by drivinPloS onee0330193https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435669biostudies-literatureACE1 does not influence cerebral Aβ degradation or amyloid plaque accumulation in 5XFAD mice.PMC12435669Jeon SPopovic JCuddy LKAlia AOVassar RfalseACE1 does not influence cerebral Aβ degradation or amyloid plaque accumulation in 5XFAD mice.Alzheimer's disease is the most common form of dementia, and multiple lines of evidence support the relevance of Aβ deposition and amyloid plaque accumulation in the neurotoxicity and cognitive decline in AD. Rare mutations in angiotensin-converting-enzyme-1 have been highly associated with late onset AD patients; however, the mechanism for ACE1 mutation in AD pathogenesis is unknown. While numerous studies have shown that ACE1 indeed catabolizes Aβ, majority of these studies were performed in vitro, and conflicting results have been reported in clinical and in vivo systems. Therefore, we further investigated this in vivo by generating and examining a novel mouse model. Specifically, we analyzed 6-month-old 5XFAD mice with ACE1 knockdown restricted to excitatory neurons, achieved by drivin2025-01-01T00:00:00Z20252026-06-01T06:22:25.257Z2026-04-08T09:48:23.2ZS-EPMC124356694095299810.1371/journal.pone.0330193