{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T22:20:36Z","timestamp":1769034036643,"version":"3.49.0"},"reference-count":57,"publisher":"Cambridge University Press (CUP)","issue":"6","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Acta Neuropsychiatr."],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0924270823000388_as1\"><jats:title>Objective:<\/jats:title><jats:p>In Alzheimer\u2019s disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-\u03b2 by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-\u03b2-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the <jats:italic>ACE<\/jats:italic> insertion\/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (<jats:italic>APOE<\/jats:italic>)-\u03f54 carrier status and blood pressure response to angiotensin modulators.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270823000388_as2\"><jats:title>Methods:<\/jats:title><jats:p>Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking <jats:italic>APOE<\/jats:italic>-\u03f54 carrier status and genotypes of the <jats:italic>ACE<\/jats:italic> insertion\/deletion polymorphism into account, along with treatment with ACEis or ARBs.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270823000388_as3\"><jats:title>Results:<\/jats:title><jats:p>For 193 patients (67.4% women, 53.4% <jats:italic>APOE<\/jats:italic>-\u03f54 carriers), the <jats:italic>ACE<\/jats:italic> insertion\/deletion polymorphism was in Hardy\u2013Weinberg equilibrium (<jats:italic>p<\/jats:italic> = 0.281), while arterial hypertension was prevalent in 80.3% (<jats:italic>n<\/jats:italic> = 124 used an ACEi, <jats:italic>n<\/jats:italic> = 21 used an ARB). ARBs benefitted mostly <jats:italic>APOE<\/jats:italic>-\u03f54 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted <jats:italic>APOE<\/jats:italic>-\u03f54 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The <jats:italic>ACE<\/jats:italic> insertion\/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270823000388_as5\"><jats:title>Conclusion:<\/jats:title><jats:p>Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.<\/jats:p><\/jats:sec>","DOI":"10.1017\/neu.2023.38","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:35:57Z","timestamp":1692696957000},"page":"346-361","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacogenetics of angiotensin modulators according to <i>APOE<\/i>-\u03f54 alleles and the <i>ACE<\/i> insertion\/deletion polymorphism in Alzheimer\u2019s 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