A major new study on Alzheimer’s disease provides previously unknown evidence of how the brain-robbing illness may originate. Moreover, it proposes that certain HIV drugs called reverse transcriptase inhibitors could be repurposed for Alzheimer’s patients.
Led by scientists from Sanford Burnham Prebys Medical Discovery Institute in San Diego, the study finds that, as suspected, Alzheimer’s is a genetic disease. But generally not inherited. Rather, it arises during a patient’s lifetime by genetic rearrangements in neurons. Sequences of DNA are copied, altered and inserted back into the genome.
The genetic rearranging isn’t random mutation, but a process that recombines DNA into different patterns. This reshuffling creates a mosaic of slightly differing cells. The immune system uses a similar process to make antibodies, but nothing like it has been seen in the human brain. The study was published in the journal Nature.
Confirmation of the findings is required, said Dr. Jerold Chun, the lead author. But Chun said testing with the HIV drugs should begin immediately. Even a low degree of effectiveness would be better than what is now available.
The study combines single and multiple-cell analytical methods to examine 13 donated human brains, some normal, some with Alzheimer’s. Its findings jibe with epidemiological data from elderly HIV patients. They have been treated with reverse transcriptase inhibitors for decades, and rarely get Alzheimer’s.
Cautious praise came from Dr. Paul Aisen, who heads the University of Southern California Alzheimer’s Therapeutic Research Institute. “The authors carefully demonstrate that there are extensive modifications to genetic material in the Alzheimer’s disease brain,” he said. “These are changes that occur with aging, rather than inherited genetic characteristics. While this is an intriguing idea, the actual contribution of this age-related genetic change remains uncertain.”
About 5.7 million Americans have Alzheimer’s, the Alzheimer’s Association said. That number is expected to double by 2060, the Centers for Disease Control and Prevention said.
In recent years, Alzheimer’s researchers have changed their view of the disease. They now say Alzheimer’s begins decades before symptoms appear. Eventually, the damage eating away at the brain becomes severe enough to affect cognition and memory. So increasingly, researchers are looking for the earliest possible signs that Alzheimer’s is developing, before mental functions are affected.
The study traces the ultimate cause to the genetic rearrangements, so blocking this reshuffling should block Alzheimer’s.