title: Angiotensin II-inhibition: effect on Alzheimer's pathology in the aged triple transgenic mouse.
abstract: Reducing excessive accumulation of amyloid-β (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies, and inhibition of angiotensin-converting enzyme (ACE) may delay onset or progression of AD. The effects of an ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Aβ and tau pathology in a triple transgenic (3xTGAD) mouse model of AD were investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6 months. Mean arterial blood pressure (MABP) was measured periodically and mice were assessed behaviourally. Aβ, phospho-tau, amyloid precursor protein (APP) and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3 months in the ACE-I group and at 3 months in the ARB group, compared to vehicle. Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze, nor were Aβ, tau immunolabelling or APP levels altered. ACE-I significantly reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not affect Aβ or phospho-tau accumulation in brains of aged 3xTGAD mice.
authors.forename: Linda
authors.initials: L
authors.lastname: Ferrington
authors.forename: Laura E
authors.initials: LE
authors.lastname: Palmer
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Horsburgh
authors.forename: Paul At
authors.initials: PA
authors.lastname: Kelly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe