Plasma Angiotensin-Converting Enzyme in Alzheimer's Disease

Article type: Research Article

Authors: Vardy, Emma R.L.C.^{a; 1} | Rice, Penny J.^a | Bowie, Peter C.W.^b | Holmes, John D.^c | Catto, Andrew J.^{a; 2} | Hooper, Nigel M.^{d; *}

Affiliations: [a] Divison of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK | [b] Sheffield Care Trust, Grenoside Grange Hospital, Salt Box Lane, Sheffield, UK | [c] Academic Unit of Psychiatry and Behavioural Sciences, University of Leeds, Leeds, UK | [d] Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK

Correspondence: [*] Corresponding author: Nigel M. Hooper, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT, UK. Tel.: +44 113 343 3163; Fax. +44 113 343 5638; E-mail: [email protected].

Note: [1] Present address: Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.

Note: [2] Present address: Neurovascular Unit, Airedale National Health Service Trust, Steeton, UK.

Note: [] Communicated by Ruth Itzhaki

Abstract: The insertion allele in the gene encoding angiotensin-converting enzyme (ACE) is a risk factor for Alzheimer's disease (AD) and ACE is one of several peptidases that have the ability to degrade the neurotoxic amyloid-β peptide. ACE is a membrane-bound peptidase that is also present in a soluble form in plasma as a result of a zinc metalloprotease-mediated shedding event. Here we aimed to determine whether there is a difference in ACE in the plasma of late-onset clinically diagnosed AD patients (n = 94) as compared to age-matched non-demented control subjects (n = 188). Plasma ACE was lower in the AD subjects as compared to the controls both at baseline (p = 0.072) and after two years (p = 0.05). There was a greater reduction in plasma ACE in the AD subjects as compared to the control subjects over the two years. Plasma ACE did not correlate with cognitive function. The observed reduction in plasma ACE in AD may reflect a general decrease in the zinc metalloprotease-mediated shedding of a subset of membrane-bound proteins.

Keywords: Alzheimer's disease, angiotensin-converting enzyme, apolipoprotein E, plasma, shedding, zinc metalloprotease

DOI: 10.3233/JAD-2009-1002

Journal: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 609-618, 2009