Solving the Puzzle of AIDS-Related Dementia

Dementia is one of the most prevalent complications among patients with late-stage HIV.

A specific neuron protein plays an important role in dementia associated with AIDS, a collaborative team from Cardiff University in Wales, United Kingdom and the University of California, Los Angeles (UCLA) has found. Dementia is one of the most prevalent complications among patients with late HIV-1.

The virus has the ability to cross the blood-brain barrier, which is why it can interfere with brain tissue. Around 30% of adults and 50% of infants with HIV experience cognitive deficits, and in the past it was thought that AIDS-related dementia was caused indirectly by HIV hurting immune cells.

C-C chemokine receptor type 5 (CCR5) has been explored in relation to HIV-1 for quite some time. However, researchers haven’t known how it impacts learning and memory. In this recent study, the Cardiff-UCLA team made a breakthrough in understanding how the neuron protein comes into play.

Interestingly, this research came about almost accidentally. When analyzing the behavior of mice at UCLA, the researchers found that some had better memories. It turns out that the animals that lacked CCR5 proteins in their neurons had these better memories. In contrast, the mice with over-expressed CCR5 protein learned at a slower pace.

“Our findings signal a major turnaround on how we imagine treating cognitive problems associated with AIDS,” Miou Zhou, PhD, a UCLA scientist, said in a news release.

Previous research already showed AIDS uses CCR5 to infect immune cells, but the researchers went a step further. Treating the mice’s brains, they introduced the part of HIV which attaches to CCR5. This resulted in worse learning and memory.

“I am still amazed that mice without CCR5 can have much better memory than normal mice,” said Alcino Silva, PhD, professor of neurobiology and psychiatry at UCLA.

These findings indicate that HIV increases the natural levels of CCR5 while inhibiting cells from plasticity function—resulting in AIDS-related dementia.

“Armed with the new knowledge that the CCR5 protein in neurons affects learning and plays a major role in AIDS-related dementia, we can now look at ways to suppress it for treatment of the disease and investigate whether its reduction can also benefit other forms of dementia and even aid recovery for stroke victims,” said Kevin Fox, PhD, a professor at Cardiff University.

There’s already a variety of CCR5 receptor antagonists on the market, such as enfuvirtide (Fuzeon) and maraviroc (Selzentry). So while novel therapies could be developed with this new information, it’s good to know that there are readily available options.

“With the available CCR5 drugs on the market this work could have broad and immediate applicability across a range of neurological diseases,” concluded Stuart Greenhill, PhD, of Aston University.

The study, “CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory,” was published in eLife.

More resources pertaining to Alzheimer’s disease and dementia can be found on Specialty Pharmacy Times' new sister site, NeurologyLive.