PT  - JOURNAL ARTICLE
AU  - Jeon, Sohee
AU  - Alia, Alia O.
AU  - Popovic, Jelena
AU  - Vassar, Robert J.
AU  - Cuddy, Leah K.
TI  - ACE1 Does Not Influence Cerebral Aβ Degradation or Amyloid Plaque Accumulation in 5XFAD Mice
AID  - 10.1101/2024.09.27.615540
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.09.27.615540
4099  - http://biorxiv.org/content/early/2024/09/30/2024.09.27.615540.short
4100  - http://biorxiv.org/content/early/2024/09/30/2024.09.27.615540.full
AB  - Alzheimer’s disease (AD) 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 (ACE1) have been highly associated with late onset AD patients; however, the mechanism for ACE1 mutation in AD pathogenesis is unknown. Given the relevance of ACE1 with AD and the strong association of Aβ to AD pathogenesis, we investigated whether ACE1 degrades Aβ and affects amyloid burden in 5XFAD mice in vivo. To investigate this, we analyzed 6-month-old 5XFAD mice with ACE1 loss of function. ACE1 loss of function was mediated either by crossing 5XFAD mice to ACE1 conditional knockout mice or administering 5XFAD mice with the ACE1 inhibitor enalapril. Our analyses revealed that ACE1 loss of function through both genetic and pharmacological methods does not affect amyloid plaque load and neuroinflammation in the hippocampus and cortex of 5XFAD mice.Competing Interest StatementThe authors have declared no competing interest.Aβ42Amyloid Beta 42 peptideACE1Angiotensin Converting Enzyme 1ACEiACE1 inhibitorADAlzheimer’s DiseaseAGTAngiotensinogenAngIAngiotensin IAngIIAngiotensin IIAPPAmyloid Precursor ProteinAT1RAngII Receptor Type 1AT2RAngII Receptor Type 2BBBBlood Brain BarrierCERCerebellumCNSCentral Nervous SystemCTXCortexFADFamilial Alzheimer’s DiseaseHPCHippocampusLC-MS/MSLiquid chromatography - tandem mass spectrometryPS1Presenilin1RASRenin Angiotensin System