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.

项目概要/摘要 阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，其特征是进行性进展 功能受损。 世界卫生组织估计全世界有 5500 万人生活 患有痴呆症的人，其中三分之二是由于 AD 引起的，预计到 2020 年这一数字将增加到 1.315 亿 2050 年。 2021 年，估计有 3840 万人感染人类免疫缺陷病毒 1 (HIV)。 相关神经认知障碍 (HAND) 是一种与 HIV 相关的常见原发性神经系统疾病 尽管联合抗逆转录病毒药物成功控制了病毒学，但中枢神经系统感染 治疗（cART）美国 50% 的 HIV 阳性人群。 年龄在50岁或以上，主要是由于成功 治疗方案可帮助艾滋病毒呈阳性的成年人在感染艾滋病毒后存活数十年。人们担心 AD 可能会发展为艾滋病毒。 普遍存在较早发病的认知缺陷或加速疾病进展的情况。 科学数据支持或反对 HIV 是否会影响 AD 认知能力下降的发生和进展。 为了解决这个关键的知识差距并检验假设，我们将使用两种 AD 小鼠模型，人类淀粉样蛋白 敲入小鼠（hAβKI）和感染嵌合HIV（EcoHIV）的Tau转基因小鼠模型。 假设 HIV 会促进 AD 小鼠模型认知能力下降，我们将使用多学科的方法。 检验假设的方法，包括行为、药理学、分子生物学和生物化学。 目标 1. 我们将使用 2 个 AD 小鼠模型（一种模仿 PLWH 的 HIV 模型）进行首次纵向研究， 以及捕获多种 AD 相关认知功能障碍的多项结果测量，以确定 EcoHIV 是否 加速 AD 小鼠认知能力下降的发生，我们还将探索其潜在机制（例如 Aβ）。 处置）。 该应用程序解决了严重的健康状况以及患有以下疾病的个人面临的新挑战 HIV 年龄和与年龄相关的神经退行性疾病：HIV 和 AD 合并症将是一个潜在的结果。 EcoHIV 会促进 AD 小鼠认知能力下降，这一知识有可能推动这一进展。 HIV 和 AD 合并症领域，因为它将表明 HIV 和 AD 不是独立的健康状况， 但当他们共病时，HIV 会干扰 AD 认知能力下降。