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血管紧张素 II 受体阻滞剂降低 Tau/Aβ42 比值:一项脑脊液生物标志物的病例对照研究。

Angiotensin II Receptor Blockers Reduce Tau/Aß42 Ratio: A Cerebrospinal Fluid Biomarkers' Case-Control Study.

作者信息

García-Lluch Gemma, Peña-Bautista Carmen, Royo Lucrecia Moreno, Baquero Miguel, Cañada-Martínez Antonio José, Cháfer-Pericás Consuelo

机构信息

Research Group in Alzheimer Disease, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.

Cátedra DeCo MICOF-CEU UCH, Universidad Cardenal Herrera-CEU, 46115 Valencia, Spain.

出版信息

Pharmaceutics. 2023 Mar 12;15(3):924. doi: 10.3390/pharmaceutics15030924.

Abstract

(1) Background: The role of antihypertensives in Alzheimer's Disease (AD) prevention is controversial. This case-control study aims to assess whether antihypertensive medication has a protective role by studying its association with amyloid and tau abnormal levels. Furthermore, it suggests a holistic view of the involved pathways between renin-angiotensin drugs and the tau/amyloidß42 ratio (tau/Aß42 ratio); (2) Methods: The medical records of the participant patients were reviewed, with a focus on prescribed antihypertensive drugs and clinical variables, such as arterial blood pressure. The Anatomical Therapeutic Chemical classification was used to classify each drug. The patients were divided into two groups: patients with AD diagnosis (cases) and cognitively healthy patients (control); (3) Results: Age and high systolic blood pressure are associated with a higher risk of developing AD. In addition, combinations of angiotensin II receptor blockers are associated with a 30% lower t-tau/Aß42 ratio than plain angiotensin-converting enzyme inhibitor consumption; (4) Conclusions: Angiotensin II receptor blockers may play a potential role in neuroprotection and AD prevention. Likewise, several mechanisms, such as the PI3K/Akt/GSK3ß or the ACE1/AngII/AT1R axis, may link cardiovascular pathologies and AD presence, making its modulation a pivotal point in AD prevention. The present work highlights the central pathways in which antihypertensives may affect the presence of pathological amyloid and tau hyperphosphorylation.

摘要

(1) 背景:抗高血压药物在阿尔茨海默病(AD)预防中的作用存在争议。本病例对照研究旨在通过研究其与淀粉样蛋白和tau异常水平的关联,评估抗高血压药物是否具有保护作用。此外,本研究还提出了肾素 - 血管紧张素药物与tau/淀粉样蛋白β42比值(tau/Aβ42比值)之间相关途径的整体观点;(2) 方法:回顾了参与研究患者的病历,重点关注所开具的抗高血压药物和临床变量,如动脉血压。采用解剖治疗化学分类法对每种药物进行分类。将患者分为两组:AD诊断患者(病例组)和认知健康患者(对照组);(3) 结果:年龄和高收缩压与患AD的较高风险相关。此外,与单纯使用血管紧张素转换酶抑制剂相比,联合使用血管紧张素II受体阻滞剂可使总tau蛋白/Aβ42比值降低30%;(4) 结论:血管紧张素II受体阻滞剂可能在神经保护和AD预防中发挥潜在作用。同样,一些机制,如PI3K/Akt/GSK3β或ACE1/AngII/AT1R轴,可能将心血管疾病与AD的存在联系起来,使其调节成为AD预防的关键点。本研究突出了抗高血压药物可能影响病理性淀粉样蛋白和tau过度磷酸化存在的核心途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e542/10059654/cd7446647b7e/pharmaceutics-15-00924-g001.jpg

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