New research offers avenue to explore relationship between Alzheimer's and HIV

by University of Nebraska-Lincoln

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UNMC researchers have published an article in Alzheimer's & Dementia detailing the creation of an animal model that helps resolve questions about the relationship between HIV and Alzheimer's disease (AD).

The work can serve as a guide for developing novel therapeutics to halt memory loss. Antiretroviral drugs have shown strong potential to prevent and slow the progression of both HIV and AD. Specific classes of HIV medications suppress brain inflammation and genetic mutations linked to Alzheimer's pathology.

The model demonstrates how the virus and amyloid beta proteins—the root cause of AD that clump together to form sticky amyloid plaques—initiate a complex chain that, along with other disease factors, drives nerve cell injury and cognitive impairments in AD pathology.

Corresponding authors Pravin Yeapuri, Ph.D., and Howard Gendelman, MD, of the UNMC Department of Pharmacology and Experimental Neuroscience (PEN), said the study is the culmination of decades of work on brain diseases following the creation of UNMC's Center for Neurovirology and Neurodegenerative Disorders in 1997.

Until now, the link between the two disease entities was obscure. But the paper has far-reaching implications, Yeapuri said, adding, "Research has already shown that certain HIV medications (nucleoside reverse transcriptase inhibitors, or NRTIs) may both lower the risk of Alzheimer's disease and significantly reduce brain inflammation."

The UNMC research team, which included Shaurav Bhattarai, Ph.D., developed a unique animal model to study questions such as:

• Does HIV affect the progression of AD, and vice versa? If so, how?
• Could an HIV-AD neurocognitive disorder, driven by different pathologies, converge to cause cognitive dysfunction?
• What is the role of aging in HIV-AD? As HIV-infected persons are living into their 70s and longer, does HIV bring added risks of neurodegenerative disease?
• Can the findings in this study lead to new therapies that will treat both diseases, and if so, how should they be studied and applied?

Bhattarai noted that people living with HIV have a higher overall risk of developing dementia compared with the general population, though direct evidence specifically linking HIV to a higher prevalence of classic Alzheimer's disease remains unknown.

The animal model overcomes a major barrier in modeling HIV-AD comorbidity by combining AD-like neurodegeneration with the capacity for human immune reconstitution, said Tsuneya Ikezu, MD, Ph.D., the Robert D. and Patricia E. Kern Professor of Neurology and director of the Molecular NeuroTherapeutics Laboratory at the Mayo Clinic.

"Developing such a model has been technically challenging because it requires precise modification and humanization of multiple genetic sequences while preserving physiological, endogenous expression of the relevant AD-associated proteins."

"The HIV-AD disease overlap is driven by persistent low viral loads and inflammation. The research uncovered specific pathways that are HIV and AD risk factors. Each, alone and together, leads to brain damage," Gendelman said. "Characterization of each opens new opportunities for therapies, specifically where antiretroviral therapy, or ART, can now be used as a treatment for both."

In the study, nerve cells were found to be most vulnerable to injury despite not being directly infected with HIV-1. This finding highlighted how HIV and AD in tandem affect the nervous system in older people.

"Specific ART component drugs can block the inflammation that can trigger both diseases," Gendelman said.

"Studies show older adults with HIV experience higher rates of overall dementia (around 2.5%) compared with uninfected persons (around 1.3%). As HIV-infected persons live longer, they become vulnerable to age-related conditions like Alzheimer's disease and vascular dementia, which are aggravated by chronic inflammation in the brain."

Publication details

Shaurav Bhattarai et al, Increased Amyloidogenic Neuronal Injury in HIV‐1–infected APP‐KI Alzheimer's disease mice, Alzheimer's & Dementia (2026). DOI: 10.1002/alz.71807

Journal information: Alzheimer's & Dementia

Key medical concepts

Alzheimer's DiseaseHIV InfectionsAmyloid beta-PeptidesInflammation

Clinical categories

NeurologyInfectious diseasesHIV & AIDSHealthy aging Provided by University of Nebraska-Lincoln Who's behind this story?

Sadie Harley

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