AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 1(2):163-177,2009

Original Article
Angiotensin-converting enzyme levels and activity in Alzheimer’s
disease: differences in brain and CSF ACE and association with ACE1

Scott Miners, Emma Ashby, Shabnam Baig, Rachel Harrison, Hannah Tayler, Elizabeth Speedy,  Jonathan A
Prince, Seth Love and Patrick G Kehoe

Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of
Bristol, Frenchay Hospital, Frenchay, Bristol BS16 1LE, UK; Department of Medical Epidemiology and
Biostatistics, Karolinska Institute, 177 77 Stockholm, Sweden

Received January 6, 2009; accepted January 12, 2009; available online January, 2009

Abstract: Angiotensin-converting enzyme (ACE) has been implicated in Alzheimer’s disease (AD): ACE1
variations influence plasma ACE and risk of AD, and ACE is increased in AD brain. We measured frontal ACE
level and activity in 89 AD and 51 control brains, and post-mortem CSF from 101 cases and 19 controls. Neuron-
specific enolase (NSE) level and Braak stage were used to indicate neuronal preservation and disease
progression. We genotyped the common ACE insertion/deletion polymorphism, rs4343, rs1800764 and rs4921.
ACE activity was elevated in AD and correlated with Braak stage. Crude ACE levels were unchanged but
adjustment for NSE suggested increased neuronal ACE production with Braak stage. Exposing SH-SY-5Y
neurons to oligomeric Aβ1-42 increased ACE level and activity, suggesting Aβ may upregulate ACE in AD. In CSF,
ACE level but not activity was reduced in AD. ACE1 genotype did not predict ACE level or activity in brain or CSF.
ACE activity and neuronal production increase in AD brain, possibly in response to Aβ. Peripheral measurements
do not reflect ACE activity in the brain. (AJTR901003).

Key Words: Angiotensin-converting enzyme; enzyme activity; Braak stage; ACE1; Alzheimer’s disease;
cerebrospinal fluid; neuron-specific enolase

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Address all correspondence to:
James Scott Miners, PhD
Clinical Science at North Bristol
University of Bristol, Frenchay Hospital
Bristol BS16 1LE, UK.
Tel: +44 117 9701212 ext 2380
Fax: +44 117 9573955