Anti-Cancer Drug Reverses Alzheimer's Disease in Mice
There may be a breakthrough when it comes to Alzheimer's disease. Scientists have discovered that an anti-cancer drug reverses memory deficits in mice that have the condition. The finding could eventually lead to better treatment in humans.
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The researchers were actually studying mice expressing human Apolipoprotein E4 (APOE4), the only established genetic risk factor for late-onset Alzheimer's disease. They also were studying mice with human APOE3 which is known not to increase the risk for Alzheimer's disease. During the course of their work, they learned that a study was published that stated that the drug bexarotene improved memory and rapidly cleared amyloid plaques from the brains of Alzheimer's model mice. They were intrigued, and decided to see whether they could independently arrive at the same findings.
Bexarotene is a compound chemically related to vitamin A. It activates Retinoic X Receptors (RXR) found everywhere in the body, including neurons and other brain cells. Once activated, the receptors bind to DNA and regulate the expression of genes that control a variety of biological processes. So far, researchers have found that increased levels of APOE are one consequence of RXR activation.
The scientists for this study treated mice with the Alzheimer's gene mutations with bexarotene. After about 10 days of beginning treatment, they found that the mice expressing human APOE3 and APOE4 were able to perform as well in cognitive tests as their non-Alzheimer's counterparts.
"While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the insterstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains," said Iliya Lefterov, co-author of the new study, in a press release.
The researchers believe that the drug works through a different biological process. It's possible that it reduces soluble oligomers which, like the plaques, are composed of the toxic amyloid beta protein fragments. However, these oligomers are composed of smaller amounts of amyloid beta and, unlike the plaques, are able to move.
The findings could lead to future research with the drug. In addition, it may provide a way to better treat Alzheimer's disease.
The findings are published in the journal Science.