From Inflammation to Intervention: Macrophage-Driven Mechanisms of Neurocognitive Impairment in HIV
Description: As people with HIV (PWH) live longer thanks to effective treatments, many are now reaching older ages where memory and thinking problems, known as neurocognitive impairment (NCI), are becoming more common. In fact, about half of all PWH experience some form of NCI, even when their HIV is well-controlled with medication. These problems can include difficulties with memory, attention, and decision-making, and they can significantly affect quality of life. This research project explores why NCI happens in aging PWH and how we might prevent or treat it. Scientists have noticed that some PWH develop brain changes similar to those seen in Alzheimer’s disease, such as the buildup of a sticky protein called amyloid-beta. However, it’s still unclear why this happens and how it leads to cognitive problems. Our study focuses on special immune cells in the brain called macrophages, which include microglia and other related cells. These cells help keep the brain healthy by cleaning up waste and responding to infections. But in PWH, these cells may become overactive and less effective at clearing harmful proteins like amyloid-beta, possibly contributing to brain damage and NCI. We aim to 1) Understand how brain macrophages and amyloid buildup are linked to memory problems in older PWH by studying donated brain tissue; 2) Identify signs of inflammation in blood and spinal fluid that could help doctors detect early brain changes before symptoms appear; and 3) Test whether existing drugs can “reprogram” macrophages to become better at clearing amyloid and reducing inflammation, using advanced lab models made from human cells. By combining brain tissue studies, blood tests, and lab experiments, this project hopes to uncover new ways to detect, understand, and treat memory problems in aging PWH. If successful, it could lead to new therapies that improve brain health and quality of life for thousands of people living with HIV.
Amount: $270,000
Start date: 2026-03-01
Investigators: Johannes Schlachetzki, Johannes Schlachetzki
Institution: The Regents of the University of California; University of California San Diego
Funded outputs count: 0
Funder award ID: g97hjg
OpenAlex ID: G3175204875