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Am J Transl Res 2012;4(2):151-164
Original Article
Angiotensin II-inhibition: effect on Alzheimer’s pathology in the aged
triple transgenic mouse
Linda Ferrington, Laura E Palmer, Seth Love, Karen J Horsburgh, Paul AT Kelly, Patrick G Kehoe
Cerebral Pharmacology Laboratory, Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George
Square, Edinburgh, EH8 9JZ, United Kingdom; Dementia Research Group, John James Laboratories, School of
Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, BS16 1LE, United Kingdom; Department of
Neuropathology, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay
Hospital, Bristol, BS16 1LE, United Kingdom; Centre for Cognitive Aging and Cognitive Epidemiology, Centre for
Neuroregeneration, Chancellor’s building, 49 Little France Crescent, University of Edinburgh, Edinburgh, EH16
4SB, United Kingdom
Received March 27, 2012; accepted April 6, 2012; Epub April 12, 2012; Published April 30, 2012
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.
(AJTR1203004).
Keywords: Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, hypertension, triple
transgenic mouse model, Alzheimer’s disease, amyloid-beta
Address all correspondence to:
Dr. Linda Ferrington
Cerebral Pharmacology Laboratory
Centre for Cognitive and Neural Systems
University of Edinburgh, 1 George Square
Edinburgh, EH8 9JZ, United Kingdom.
Tel: +44 (0)131 650 4571; Fax: +44 (0)131 651 1835
E-mail: Paul.Kelly @ ed.ac.uk, Linda.Ferrington @ ed.ac.uk
Original Article
Angiotensin II-inhibition: effect on Alzheimer’s pathology in the aged
triple transgenic mouse
Linda Ferrington, Laura E Palmer, Seth Love, Karen J Horsburgh, Paul AT Kelly, Patrick G Kehoe
Cerebral Pharmacology Laboratory, Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George
Square, Edinburgh, EH8 9JZ, United Kingdom; Dementia Research Group, John James Laboratories, School of
Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, BS16 1LE, United Kingdom; Department of
Neuropathology, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay
Hospital, Bristol, BS16 1LE, United Kingdom; Centre for Cognitive Aging and Cognitive Epidemiology, Centre for
Neuroregeneration, Chancellor’s building, 49 Little France Crescent, University of Edinburgh, Edinburgh, EH16
4SB, United Kingdom
Received March 27, 2012; accepted April 6, 2012; Epub April 12, 2012; Published April 30, 2012
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.
(AJTR1203004).
Keywords: Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, hypertension, triple
transgenic mouse model, Alzheimer’s disease, amyloid-beta
Address all correspondence to:
Dr. Linda Ferrington
Cerebral Pharmacology Laboratory
Centre for Cognitive and Neural Systems
University of Edinburgh, 1 George Square
Edinburgh, EH8 9JZ, United Kingdom.
Tel: +44 (0)131 650 4571; Fax: +44 (0)131 651 1835
E-mail: Paul.Kelly @ ed.ac.uk, Linda.Ferrington @ ed.ac.uk
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