麻豆传媒

Brain cells聽are reshuffling their own聽DNA. The finding may explain how Alzheimer鈥檚 disease develops and pave the way for new treatments using existing HIV drugs.

Most drugs聽for treating聽Alzheimer鈥檚 disease are designed to clear out clumps of beta-amyloid protein that build up in the brain聽of people with the condition. But they have had in clinical trials so far.

While studying the gene responsible for making beta-amyloid 鈥� called APP 鈥� at Sanford Burnham Prebys Medical Discovery Institute in California and his colleagues discovered something strange. The gene appeared to be able to reshuffle its DNA, allowing it to take thousands of different forms.

The team found about 10 times more variants of the APP gene in brain cells from people with Alzheimer鈥檚 disease than without. These different forms were able to produce a range of toxic proteins in addition to beta-amyloid.

The finding may explain why Alzheimer鈥檚 drugs that specifically target beta-amyloid have had limited success, says Chun. 鈥淭hey may be missing thousands of other toxic products that are a bit different or maybe very different,鈥� he says.

Shapeshifting gene

At the moment, it鈥檚 unclear why the APP gene is able to morph into different forms. In healthy people, it may give the brain greater flexibility by letting it produce a wider repertoire of signaling proteins, says Chun.

We also don鈥檛 know why the gene seems to shapeshift more in the brains of people with Alzheimer鈥檚 disease, says Chun. So far, his team鈥檚 research suggests that it is linked to the activity of a group of enzymes called reverse transcriptases.

The same enzymes are already well-known in the context of HIV, as they are responsible for letting the virus insert itself in infected people鈥檚 DNA. It鈥檚 possible that existing HIV drugs that block these enzymes聽 鈥� called reverse transcriptase inhibitors 鈥� may also be useful for treating Alzheimer鈥檚 disease, says Chun.

This idea is supported by the observation that elderly HIV patients who have been on long-term treatment with reverse transcriptase inhibitors seem rarely to develop Alzheimer鈥檚 disease. However, clinical trials will be needed to prove it, says Chun.

His team is currently testing the effectiveness of聽already-available reverse transcriptase inhibitors for HIV in mouse models of Alzheimer鈥檚 disease, as well as planning possible future trials in humans. 鈥淭he great thing about these drugs is that many of them have been used in HIV patients for decades, so we already know they鈥檙e safe,鈥� he says.