ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
Population-based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Alzheimer's disease target and drug discovery by leveraging multiomics and electronic health data.Nature neuroscience · 2026Article
- PPAR-γ modulation restores the adiponectin-AMPK-AKT axis to attenuate metabolic stress-associated alzheimer's pathology.Molecular biology reports · 2026Article
- Virtual screening of drugs against multiple targets of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- The application of telmisartan in central nervous system disorders.Pharmacological reports : PR · 2025Review
- Article
- Drug repurposing for Alzheimer's disease and other neurodegenerative disorders.Nature communications · 2025Review
- Alzheimer's Disease: Exploring Pathophysiological Hypotheses and the Role of Machine Learning in Drug Discovery.International journal of molecular sciences · 2025Review
- Ras, RhoA, and vascular pharmacology in neurodevelopment and aging.Neurochemistry international · 2024Review
- Article
- Sex-stratified genome-wide association and transcriptome-wide Mendelian randomization studies reveal drug targets of heart failure.Cell reports. Medicine · 2024Article
- Investigating the Impact of Selective Modulators on the Renin-Angiotensin-Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents.International journal of molecular sciences · 2023Review
- Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia.Pharmaceutics · 2023Review
- Behavioral and Proteomic Studies Reveal Methylglyoxal Activate Pathways Associated with Alzheimer's Disease.ACS pharmacology & translational science · 2023Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
introductionAfrican Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials.
methodsWe conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan-Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD.
resultsWe identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65-0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89-1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs. Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD. DISCUSSION: Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. HIGHLIGHTS: Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR-γ agonistic properties with beneficial anti-diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.
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