amyloid beta

Aging HIV patients at risk for Alzheimers-like dementia
21 July 2004, Rebecca Vesely, San Mateo County Times

As HIV patients age, they may be at risk of developing chronic dementia similar to Alzheimer's disease, according to a study presented Tuesday by researchers at University of California at San Francisco and the San Francisco Veterans Affairs Medical Center.

The study is part of a burgeoning field in HIV research: the complications people living with the virus will face as they grow old.

"What we're worried about is a kind of slow, chronic dementia we haven't seen before in HIV patients," said lead researcher Lynn Pulliam, a UCSF professor of laboratory medicine.

In the aging process, a protein called amyloid beta is produced that damages brain cells. Normally, an enzyme called neprilysin breaks down amyloid beta, preventing the damage.

However in HIV patients, an HIV-associated protein called Tat blocks neprilysin, allowing amyloid beta to accumulate, according to the study.

Like in Alzheimer's disease, the HIV researchers believe unchecked accumulation of amyloid beta in combination with other factors, including genetics, can result in a slow and devastating memory loss.

"The brain is a reservoir for HIV," Pulliam said. "Even if the virus is not detected in the blood, it remains in the brain where amyloid beta accumulates with age."

Antiretroviral drugs don't appear to play a role in slowing the dementia, Pulliam said. And the longer a patient had HIV, the more amyloid beta accumulated, regardless of age.

For the study, Pulliam and fellow researchers applied synthetic Tat to normal human brain cells that contain the enzyme neprilysin. They found a 125 percent increase in the damaging amyloid beta in the brain cells treated with Tat.

They also stained brain sections from autopsies of 14 HIV-infected people age 31 to 58 with amyloid beta antibodies. They found an increase in amyloid beta in these patients compared to an HIV-negative control group.

The findings were presented at the International Conference on Alzheimer's Disease in Philadelphia on Tuesday.

Dr. Kathleen Clanon, medical director for HIV services at the Alameda County Medical Center in Oakland, said she is seeing memory loss and other health problems-- high cholesterol, arthritis and diabetes, to name a few-- in her aging HIV patients.

"People with HIV are acquiring all the same problems that come with aging but at an accelerated rate," Clanon said.

Clanon said the UCSF findings make sense because of HIV presence in the brain. A common complaint among her patients is with memory, such as forgetfulness, not being able to concentrate all the way through a movie or having a fact or name on the tip of their tongue but being unable to access the information.

This slow memory loss among HIV patients is very different from what physicians saw in AIDS patients at the start of the epidemic, where acute dementia would develop in the final months of life, Clanon said.

It's unclear whether new treatments for Alzheimer's patients, such as Aricept, which can temporarily hold off Alzheimer's onset, could help aging HIV patients, Pulliam said. About 40,000 people are diagnosed with HIV nationwide each year.

Life-saving antiretroviral drugs have only been in widespread use in the United States since the mid-1990s, so big questions remain about the long-term effects from both the medications and the virus.

"No one knows what's going to happen," Clanon said. "We have no choice but to live through it together."

---

From the Daily HIV/AIDS Report at KaiserNetwork.org

[Jul 23, 2004]

HIV-positive people may be at risk for developing chronic dementia similar to Alzheimer's disease, according to a study presented on Tuesday at the International Conference on Alzheimer's Disease by researchers from the University of California-San Francisco and the San Francisco Veterans Affairs Medical Center, the Oakland Tribune reports. Amyloid beta, a protein that is produced during the aging process that can damage brain cells, is normally broken down by the neprilysin enzyme. However, in HIV-positive people, the HIV-associated protein Tat blocks neprilysin and amyloid can then accumulate, according to the study. UCSF professor Lynn Pulliam and colleagues applied synthetic Tat to normal human brain cells that contained neprilysin and found a resulting 125% increase in amyloid. According to Pulliam, an accumulation of unchecked amyloid, in combination with factors such as genetics, can result in a "slow and devastating" memory loss similar to Alzheimer's. "What we're worried about is a kind of slow, chronic dementia we haven't seen before in HIV patients," Pulliam said. She added that even if HIV is not detected in the blood, the virus can remain in the brain where amyloid will accumulate as a patient ages. Dr. Kathleen Clanon, medical director of HIV services at the Alameda County Medical Center, said that aging HIV-positive people are "acquiring all the same problems that come with aging but at an accelerated rate." However, Clanon said that the slow memory loss is very different from the acute dementia seen in patients during the final months of life before the advent of antiretroviral drug treatment. Although new treatments such as Aricept can temporarily delay the onset of Alzheimer's, Pulliam said that it is unclear whether they would be effective in HIV-positive people (Vesely, Oakland Tribune, 7/21).

Second Study

Antiretroviral drugs may block an enzyme that helps break down amyloid and insulin, according to another study presented at the conference (Burling, Philadelphia Inquirer, 7/23). Dr. Cristian Achim of the University of Pittsburgh and colleagues examined the brains of 160 people who had died of AIDS-related illnesses and who had used antiretroviral drugs. The researchers found that two-thirds of those studied had deposits of amyloid similar to the levels seen in people with Alzheimer's (Reuters, 7/22). The researchers found significant amounts of amyloid in the brains of patients who had used both older and newer antiretroviral drugs. Doctors treating HIV-positive people should be "especially careful" in monitoring patients for signs of dementia and diabetes, the researchers said (Philadelphia Inquirer, 7/23). "The current adult HIV patient population in the [United States] stands a good chance of surviving the virus, which means they will become affected by many of the disorders associated with later stages in life," Achim said, adding, "Although these results are preliminary, it is plausible to hypothesize that beta-amyloid brain deposits will only increase in the aging HIV population on prolonged anti-viral therapy." The researchers plan to test the hypothesis using brain imaging techniques to measure the accumulation of amyloid beta (Conference release, 7/22).