Effects of hypertension and anti-hypertensive treatment on Aβ plaque load, Aβ–synthesising and –degrading enzymes in frontal cortex

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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.
Original languageEnglish
Pages (from-to)1191-1203
Number of pages12
JournalJournal of Alzheimer's Disease
Volume50
Issue number4
Early online date19 Jan 2016
DOIs
Publication statusPublished - 22 Feb 2016

Keywords

  • Alzheimer’s disease
  • amyloid β protein
  • anti-hypertensive
  • hypertension
  • β-secretase
  • BACE
  • y-secretase
  • angiotensin-converting enzyme

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