Phosphodiesterase-5 Inhibition and Alzheimer's Disease Risk: A Mendelian Randomisation Study.

IF 7.1 1区医学 Q1 CELL BIOLOGY

Aging Cell Pub Date : 2025-10-13 DOI:10.1111/acel.70265

Marta Alcalde-Herraiz, Benjamin Woolf, Junqing Xie, Emma Anderson, Dipender Gill, Ioanna Tzoulaki, Laura M Winchester, James Yarmolinsky, Daniel Prieto-Alhambra, Danielle Newby

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引用次数: 0

Abstract

While preclinical studies suggest that Phosphodiesterase 5 (PDE5) inhibition may reduce cognitive impairment, findings from observational studies on whether PDE5 inhibitors reduce Alzheimer's disease (AD) risk have been inconsistent. We performed a two-sample cis-Mendelian Randomisation (MR) analysis to estimate the causal effect of PDE5 inhibition on AD risk. The analysis was performed across four different genome-wide association studies (GWAS) of AD to enhance reliability through triangulation. Additionally, a sex-stratified MR analysis using data from UK Biobank was performed to assess potential sex-specific effects. No evidence of a causal association between PDE5 inhibition and AD risk was found in the main analyses. Similar findings were obtained in the sex-stratified analysis. Our study uses genetic data to triangulate the evidence and suggests that PDE5 inhibitors are unlikely to decrease the risk of AD. Further research is needed to thoroughly understand the impact of PDE5 inhibitors on the risk of Alzheimer's disease.

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磷酸二酯酶-5抑制与阿尔茨海默病风险：一项孟德尔随机研究

虽然临床前研究表明抑制磷酸二酯酶5 （PDE5）可能减轻认知障碍，但关于PDE5抑制剂是否降低阿尔茨海默病（AD）风险的观察性研究结果并不一致。我们进行了一项双样本顺式孟德尔随机化（MR）分析，以估计PDE5抑制对AD风险的因果影响。该分析是在四种不同的AD全基因组关联研究（GWAS）中进行的，通过三角测量来提高可靠性。此外，使用来自UK Biobank的数据进行性别分层MR分析，以评估潜在的性别特异性影响。在主要分析中没有发现PDE5抑制与AD风险之间存在因果关系的证据。在性别分层分析中也得到了类似的结果。我们的研究使用遗传数据对证据进行三角分析，并表明PDE5抑制剂不太可能降低AD的风险。需要进一步的研究来彻底了解PDE5抑制剂对阿尔茨海默病风险的影响。

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来源期刊

Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology

自引率

2.60%

发文量

212

期刊介绍： Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.