Weill Cornell Medicine researchers have identified genetic signatures in neurons derived from skin cells of people living with HIV that may be linked to cognitive impairment. The study, published in JCI Insight on December 1, used fibroblasts collected from six virologically suppressed individuals with HIV and seven matched controls without HIV. These cells were reprogrammed into neurons using a technique that preserves age-related characteristics.
The research found notable differences in gene activity between the two groups. Some of these differences were similar to those observed in previous studies of post-mortem brain tissue from people with and without HIV, while others were newly discovered.
"These findings give us a foundation for future studies of how certain genes and biological pathways may contribute to this form of cognitive impairment," said Dr. Teresa H. Evering, senior author of the study and assistant professor at Weill Cornell Medicine.
HIV can enter the central nervous system after infection and persist even when antiretroviral therapy suppresses it in the blood. This chronic presence can lead to memory issues, concentration difficulties, mood changes, and slowed movements due to ongoing inflammation.
Despite advances in treatment that suppress the virus, neurocognitive disorders still affect between 25% and 50% of people living with HIV globally. The prevalence is declining among well-treated patients but remains a significant concern.
Current challenges in studying how HIV affects neurons have limited progress toward treatments for related cognitive problems. The new model developed by Dr. Evering's team allows for examination of neuron-specific effects while retaining donor age characteristics—important for understanding conditions associated with aging.
Researchers noted that gene expression changes seen in neurons derived from skin cells are likely due to systemic effects of HIV rather than direct exposure within the brain itself. Among key findings was increased activity of the inflammatory gene IFI27 in participants with HIV; three other genes—FOXL2NB, FOXL2, and LINC01391—were less active and linked to cognitive impairment.
Further research will focus on these genes’ roles using more complex models and larger participant groups.
