ACE1 does not influence cerebral Aβ degradation or amyloid plaque accumulation in 5XFAD mice.

Abstract

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 driving Cre recombinase expression under the CamKIIα promoter. These mice were generated by crossing 5XFAD mice to ACE1 conditional knockout mice expressing Cre specifically in excitatory neurons. Our analyses revealed that neuronal ACE1 knockdown does not significantly affect amyloid plaque load and neuroinflammation in the hippocampus and cortex of 5XFAD mice at 6-months of age.