Experimental Drug Reverses Amyloid Toxicity in Mouse Alzheimer's Disease Model

Continuing this line of research, the investigators reported in the November 28, 2012, issue of the Journal of Neuroscience that the drug neutralized the depressant effects of beta-amyloid protein and the related human pancreatic protein amylin on hippocampal long-term potentiation (LTP) in the brains of mice. Furthermore, they examined whether depressed levels of LTP observed in transgenic mice, which overexpress amyloid precursor protein (TgCRND8), could be restored with AC253.

Results revealed that preapplication of AC253 blocked beta-amyloid and human amylin-induced reduction of LTP without affecting baseline transmission or LTP on its own. In contrast to wild-type controls, where robust LTP was observed, six- to 12-month-old TgCRND8 mice show blunted LTP that was significantly enhanced by application of AC253.

The data demonstrated that the effects of beta-amyloid and human amylin on LTP were expressed via the amylin receptor; moreover, blockade of this receptor increased LTP in transgenic mice that showed increased brain amyloid burden.

"This is very important because it tells us that drugs like this might be able to restore memory, even after Alzheimer's disease may have set in," said senior author Dr. Jack H. Jhamandas, professor of neurology at the University of Alberta. "I think what we discovered may be part of the solution, but I can not say it will be the solution. There is a long list of drugs and approaches that have not panned out as expected in the fight against Alzheimer's. I do not think one drug or approach will solve Alzheimer's disease because it is a complicated disease, but I am cautiously optimistic about our discovery and its implications."

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