Title | Effects of Hypertension and Anti-Hypertensive Treatment on Amyloid-β (Aβ) Plaque Load and Aβ-Synthesizing and Aβ-Degrading Enzymes in Frontal Cortex. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Ashby, EL, Miners, JS, Kehoe, PG, Love, S |
Journal | J Alzheimers Dis |
Volume | 50 |
Issue | 4 |
Pagination | 1191-203 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Aged, 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. |
DOI | 10.3233/JAD-150831 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26836178 |
Grant List | / / Medical Research Council / United Kingdom |