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Biological Chemistry

Drug Eases Alzheimer's In Mice

Treatment reduces pathological hallmarks of disease

by Sophie L. Rovner
March 8, 2006

The experimental drug AF267B improves memory and reduces brain pathology in a transgenic mouse model of Alzheimer???s disease, according to University of California, Irvine, neurobiologist Frank M. LaFerla and colleagues (Neuron 2006, 49, 671).

As the disease develops in humans and in the team???s transgenic mice, amyloid plaques and neurofibrillary tangles of tau protein accumulate in the brain; levels of the neurotransmitter acetylcholine also decline. AF267B mimics the missing neurotransmitter. When the drug binds to acetylcholine binding sites known as M1 muscarinic receptors in the transgenic mice, levels of α-secretase increase. This enzyme limits production of amyloid-β and therefore prevents the development of both plaques and tangles.

LaFerla says AF267B is the first treatment that reduces levels of both of these pathological hallmarks of Alzheimer???s. A clinical trial to assess the compound's safety in humans is under way. UC Irvine neurobiologist James L. McGaugh says the work ???suggests the exciting prospect of possibly preventing the development of Alzheimer???s disease.???

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