AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2011;3(1):73-80

Original Article
ACE variants and association with brain Aβ levels in Alzheimer’s
disease

J. Scott Miners, Merryn Raiker, Seth Love, Patrick G. Kehoe

Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of
Bristol, BS16 1LE, UK; Department of Neuropathology, Institute of Clinical Neurosciences, Clinical Science at
North Bristol, University of Bristol, BS16 1LE, UK.

Received: Aeptember 21, 2010; accepted: September, 2010; Epub: September, 2010; Published: January 1, 2011

Abstract: ACE is a candidate gene for Alzheimer’s disease (AD) and associations have been reported between
ACE variants and plasma ACE levels, AD risk, AD age at onset of disease and cerebrospinal fluid levels of Aβ.
Despite evidence that ACE can degrade Aβ, the relationships between ACE variants and the levels of different
types of Aβ in the brain are not known. We have investigated the relationship between AD-associated ACE
variants, for which the associations with brain activity of ACE were previously analysed, and brain homogenate
levels of soluble, insoluble and oligomeric Aβ. Reported AD risk variants in the ACE indel (rs1799752) and its
‘proxy’ rs4343 were significantly associated with soluble Aβ level in AD only (p=0.001), as was rs1800764 but
less so (p=0.014). In contrast, insoluble Aβ was associated with ACE indel and rs4343 variants in controls only (p
< 0.01). No associations were found for oligomeric Aβ. These data indicate a complex relationship between ACE
and Aβ that differs between AD and control brains. (AJTR1009001).

Key words: Alzheimer’s disease; angiotensin; ACE; amyloid; neuropathology; soluble Aβ; insoluble Aβ; SNP;
association; Aβ degrading enzyme; cerebral blood flow; hypertension

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Address all correspondence to:
Patrick G. Kehoe, PhD
Dementia Research Group
Institute of Clinical Neurosciences
Clinical Science at North Bristol
University of Bristol, BS16 1LE, UK.
Tel: +44-117-340-6607
E-mail:
Patrick.Kehoe@bristol.ac.uk