Journal of Alzheimer's Disease
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Home > Effects of Hypertension and Anti-Hypertensive Treatment on Amyloid-β (Aβ) Plaque Load and Aβ-Synthesizing and Aβ-Degrading Enzymes in Frontal Cortex.

TitleEffects of Hypertension and Anti-Hypertensive Treatment on Amyloid-β (Aβ) Plaque Load and Aβ-Synthesizing and Aβ-Degrading Enzymes in Frontal Cortex.
Publication TypeJournal Article
Year of Publication2016
AuthorsAshby, EL, Miners, JS, Kehoe, PG, Love, S
JournalJ Alzheimers Dis
Volume50
Issue4
Pagination1191-203
Date Published2016
ISSN1875-8908
KeywordsAged, Aged, 80 and over, Amyloid Precursor Protein Secretases, Antihypertensive Agents, Female, Frontal Lobe, Humans, Hypertension, Immunohistochemistry, Insulysin, Male, Neprilysin, Peptidyl-Dipeptidase A, Plaque, Amyloid, Retrospective Studies
Abstract

Epidemiological data associate hypertension with a predisposition to Alzheimer's disease (AD), and a number of postmortem and in vivo studies also demonstrate that hypertension increases amyloid-β (Aβ) pathology. In contrast, anti-hypertensive medications reportedly improve cognition and decrease the risk of AD, while certain classes of anti-hypertensive drugs are associated with decreased AD-related pathology. We investigated the effects of hypertension and anti-hypertensive treatment on Aβ plaque load in postmortem frontal cortex in AD. Aβ load was significantly increased in hypertensive (n = 20) relative to normotensive cases (n = 62) and was also significantly higher in treated (n = 9) than untreated hypertensives (n = 11). We then looked into mechanisms by which hypertension and treatment might increase Aβ load, focusing on Aβ-synthesizing enzymes, β- and γ-secretase, and Aβ-degrading enzymes, angiotensin-converting enzyme (ACE), insulin-degrading enzyme (IDE) and neprilysin. ACE and IDE protein levels were significantly lower in hypertensive (n = 21) than normotensive cases (n = 64), perhaps translating to decreased Aβ catabolism in hypertensives. ACE level was significantly higher in treated (n = 9) than untreated hypertensives (n = 12), possibly reflecting feedback upregulation of the renin-angiotensin system. Prospective studies in larger cohorts stratified according to anti-hypertensive drug class are needed to confirm these initial findings and to elucidate the interactions between hypertension, anti-hypertensive treatments, and Aβ metabolism.

DOI10.3233/JAD-150831
Alternate JournalJ. Alzheimers Dis.
PubMed ID26836178
Grant List / / Medical Research Council / United Kingdom
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