HIV-1 and Alzheimer’s disease: Comorbidity

HIV-1 和阿尔茨海默病：合并症

• 批准号: 10760712
• 负责人: Khalid Benamar
• 金额: $ 40.7万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10760712
• 关键词: Acceleration; Address; Adult; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-Protein; Animal Model; Area; Behavioral; Biochemistry; Brain; Case Study; Central Nervous System Infections; Characteristics; Cognitive; Cognitive deficits; Data; Dementia; Disease Progression; Economics; Goals; HIV; HIV Infections; HIV Seropositivity; HIV diagnosis; HIV-1; HIV-associated neurocognitive disorder; Health; Human; Impaired cognition; Individual; Knock-in Mouse; Knowledge; Longitudinal Studies; Medical Care Costs; Modeling; Molecular Biology; Mus; Neurodegenerative Disorders; Neurofibrillary Tangles; Onset of illness; Outcome; Outcome Measure; Pathology; Persons; Population; Reporting; Research; Research Personnel; Sample Size; Senile Plaques; Synapses; Testing; Therapeutic Studies; Transgenic Mice; Treatment Protocols; World Health Organization; age related neurodegeneration; aged; antiretroviral therapy; biological systems; cognitive function; comorbidity; early onset; interdisciplinary approach; mouse model; nervous system disorder; neurodegenerative dementia; neuropathology; pharmacologic; public health relevance; tau Proteins; tool

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by a progressive impairment of cognitive functions. The World Health Organization estimates that 55 million people worldwide live with dementia, of which two-thirds are due to AD, and this number is expected to increase to 131.5 million by 2050. In 2021 an estimated 38.4 million people were living with Human immunodeficiency virus-1 (HIV). HIV- associated neurocognitive disorder (HAND) is a common primary neurological disorder associated with HIV infection of the central nervous system, despite successful virologic control with combination antiretroviral therapy (cART). 50% of the US HIV-positive population is aged 50 years or older, mainly due to the successful treatment regimens helping HIV-positive adults survive for decades with HIV. There is concern AD may become prevalent with an earlier onset of cognitive deficit or accelerate the disease progression. Currently, there are no scientific data to support or oppose if HIV can affect the onset and progression of AD cognitive decline. To address this critical knowledge gap and test the hypothesis, we will use two AD mouse models, human amyloid knock-in mouse (hAβKI) and Tau transgenic mice models infected with chimeric HIV (EcoHIV). Our central hypothesis is that HIV promotes the onset of cognitive decline in AD mice models. We will use a multidisciplinary approach to test the hypothesis, including behavioral, pharmacological, molecular biology, and biochemistry. Aim 1. We will perform the first longitudinal studies using 2 AD mouse models, an HIV model that mimics PLWH, and multiple outcome measures capturing several AD-associated cognitive dysfunctions to determine if EcoHIV accelerates the onset of cognitive decline in AD mice. We will also explore the potential mechanism (e.g., Aβ disposition). This application addresses critical health conditions and a new challenge that looms as individuals living with HIV age and reach age-related neurodegenerative diseases: HIV and AD comorbidity. A potential outcome will be that EcoHIV promotes the onset of cognitive decline in AD mice. This knowledge has the potential to advance the field of HIV and AD comorbidity because it will show that HIV and AD are not independent health conditions, but when they are comorbid, HIV can interfere with AD cognitive decline onset.

项目摘要/摘要 阿尔茨海默病(AD)是一种破坏性的神经退行性疾病，其特征是进行性 认知功能受损。 世界卫生组织估计，全世界有5500万人生活在 患有痴呆症，其中三分之二是由于阿尔茨海默氏症，这一数字预计到2019年将增加到1.315亿 2050年。2021年，估计有3840万人携带人类免疫缺陷病毒-1(HIV)。艾滋病毒-- 相关性神经认知障碍(HAND)是与HIV相关的一种常见的原发神经疾病 中枢神经系统感染，尽管用联合抗逆转录病毒成功地进行了病毒学控制 治疗(购物车)。美国50%的艾滋病毒阳性人口 年龄在50岁或以上，主要是由于成功 治疗方案帮助艾滋病毒阳性的成年人在感染艾滋病毒的情况下存活数十年。人们担心广告可能会成为 流行于较早出现认知缺陷或加速疾病进展。目前，没有 科学数据支持或反对HIV是否可以影响AD认知功能下降的发生和发展。至 解决这一关键的知识差距并检验假设，我们将使用两个AD小鼠模型，人类淀粉样蛋白 转基因小鼠(haβki)和Tau转基因小鼠感染嵌合艾滋病毒(EcoHIV)的模型。我们的中央 假说是HIV促进了AD模型小鼠认知功能的下降。我们将使用多学科的 检验假说的方法，包括行为学、药理学、分子生物学和生物化学。 目的1.我们将使用两个AD小鼠模型进行第一次纵向研究，这是一个模仿PLWH的HIV模型， 多项结果测量捕捉了几种与AD相关的认知功能障碍，以确定EcoHIV 加速阿尔茨海默病小鼠的认知能力下降。我们还将探索潜在的机制(例如，Aβ 处置)。 这个应用程序解决了严重的健康状况和一个新的挑战 艾滋病毒、年龄和与年龄相关的神经退行性疾病：艾滋病毒和阿尔茨海默病的共病。一个潜在的结果将是 可能是EcoHIV促进了AD小鼠认知功能衰退的发生。这一知识具有发展的潜力。 艾滋病毒和阿尔茨海默病共病领域，因为它将表明艾滋病毒和阿尔茨海默病不是独立的健康状况， 但当它们并存时，艾滋病毒可以干扰AD认知功能下降的发病。