HIV-1 and Alzheimer’s disease: Comorbidity

项目总结/文摘

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.