Drug quickly reverses Alzheimer's symptoms in mice

U.S. researchers have found that use of a drug in mice appears to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer's disease, according to a study published online in journal Science on Thursday.The results point to the significant potential that the medication, bexarotene, has to help the roughly 5.4 million Americans suffering from the progressive brain disease, the researchers said.Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade. These experiments explored whether the medication might also be used to help patients with Alzheimer's disease, and the results were more than promising.Alzheimer's disease arises in large part from the body's inability to clear naturally-occurring amyloid beta from the brain. In 2008 Case Western Reserve University researcher Gary Landreth, professor of neurosciences at School of Medicine, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins.Landreth and his colleagues chose to explore the effectiveness of bexarotene for increasing ApoE expression. The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors, which control how much ApoE is produced.In particular, the researchers were struck by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of Alzheimer's disease. The present view of the scientific community is that small soluble forms of amyloid beta cause the memory impairments seen in animal models and humans with the disease. Within six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent; even more impressive, the effect lasted as long as three days. Finally, this shift was correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer's.Bexarotene treatment also worked quickly to stimulate the removal of amyloid plaques from the brain. The plaques are compacted aggregates of amyloid that form in the brain and are the pathological hallmark of Alzheimer's disease. Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reduction totaled 75 percent. It appears that the bexarotene reprogrammed the brain's immune cells to "eat" or phagocytose the amyloid deposits. This observation demonstrated that the drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice. "This is a particularly exciting and rewarding study because of the new science we have discovered and the potential promise of a therapy for Alzheimer's disease," said Landreth. "Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment."