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 阿尔茨海默氏病（AD）是一种毁灭性的神经退行性疾病，其特征是进行性疾病 认知功能受损。 世界卫生组织估计全球有5500万人直播 痴呆症，其中三分之二是由于广告而引起的，预计该数字将增加到1.315亿 2050年。2021年，估计有3840万人患有人类免疫缺陷病毒1（HIV）。艾滋病病毒- 相关的神经认知障碍（Hand）是与HIV相关的常见原发性神经系统疾病 感染中枢神经系统，dospite成功的病毒学控制与抗逆转录病毒联合控制 治疗（购物车）。美国HIV阳性人群的50％ 年龄50岁以上，主要是由于成功 治疗方案有助于HIV阳性成年人使用HIV存活数十年。广告可能会成为 较早发作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是否会影响AD认知下降的开始和发展。到 解决这个关键的知识差距并检验假设，我们将使用两个AD鼠标模型，即人淀粉样蛋白 敲入小鼠（HAβKI）和Tau转基因小鼠模型感染了嵌合HIV（ECOHIV）。我们的中心 假设是HIV促进了AD小鼠模型的认知下降开始。我们将使用多学科 检验假设的方法，包括行为，药物，分子生物学和生物化学。 AIM 1。我们将使用2个AD小鼠模型，一个模仿PLWH的HIV模型进行第一个纵向研究， 以及捕获几种与广告相关的认知功能障碍的多种结果措施，以确定EcoHiv是否是否 加速了AD小鼠认知下降的开始。我们还将探索潜在机制（例如Aβ 处置）。 该申请应解决关键的健康状况和新的挑战 HIV年龄和与年龄相关的神经退行性疾病：HIV和合并症。潜在的结果将 无论是Ecohiv促进了AD小鼠认知能力下降的开始。这些知识有可能进步 艾滋病毒和合并症的领域，因为它表明艾滋病毒和广告不是独立的健康状况， 但是，当它们合并时，艾滋病毒会干扰广告认知能力下降。