HIV-1 and Alzheimer’s disease: Comorbidity

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.

Grant Number: 1R21AG084378-01
NIH Institute/Center: NIH
Principal Investigator: Khalid Benamar