Angiotensin-Converting Enzyme in Cerebrospinal Fluid and Risk of Brain Atrophy

Article type: Research Article

Authors: Jochemsen, Hadassa M.^{a; b} | van der Flier, Wiesje M.^{a; c} | Ashby, Emma L.^d | Teunissen, Charlotte E.^e | Jones, Ruth E.^d | Wattjes, Mike P.^f | Scheltens, Philip^a | Geerlings, Mirjam I.^b | Kehoe, Patrick G.^d | Muller, Majon^{g; *}

Affiliations: [a] Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands | [b] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands | [c] Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | [d] Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK | [e] Department of Clinical Chemistry, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands | [f] Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands | [g] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: [*] Correspondence to: Dr. M. Muller, Department of Gerontology and Geriatrics, Leiden University Medical Center, C7Q44, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Tel.: +31 71 526 6640; E-mail: [email protected].

Abstract: Background:Higher angiotensin-converting enzyme (ACE) activity might increase the risk of Alzheimer's disease by increasing blood pressure, and subsequent development of cerebral small vessel disease (CSVD). Yet, it may also decrease this risk, as it functions to degrade amyloid-β, thereby reducing brain atrophy. Objective:To examine the cross-sectional associations of serum and cerebrospinal fluid (CSF) ACE protein levels and activity with brain atrophy and CSVD in a memory clinic cohort. Methods:In 118 subjects from the memory clinic based Amsterdam Dementia Cohort (mean age 66 ± 8 years), ACE protein levels (ng/ml) and activity in CSF and serum were investigated. Poisson regression analyses were used to associate ACE measurements with rated global cortical atrophy, medial temporal lobe atrophy, lacunar infarcts, white matter hyperintensities, and microbleeds on brain MRI. Results:Higher CSF ACE activity was associated with a reduced risk of global brain atrophy. The relative risk (95% CI) of having global cortical atrophy ≥2 per SD increase in CSF ACE activity was 0.67 (0.49; 0.93). ACE levels were not significantly related to measures of CSVD. Conclusions:These results show that high ACE might have protective effects on the brain. This could suggest that ACE inhibitors, which may lower CSF ACE levels, are not preferred as antihypertensive treatment in patients at risk for Alzheimer's disease.

Keywords: Alzheimer's disease, angiotensin-converting enzyme, brain atrophy, cerebral small vessel disease, hypertension

DOI: 10.3233/JAD-131496

Journal: Journal of Alzheimer's Disease, vol. 44, no. 1, pp. 153-162, 2015