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Brain enzyme is double whammy for Alzheimer's disease
Date:8/20/2012

LA JOLLA, Calif., August 20, 2012 The underlying causes of Alzheimer's disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that's toxic to nerve cells. β-amyloid is formed by the activity of several enzymes, including one called BACE1. Most Alzheimer's disease patients have elevated levels of BACE1, which in turn leads to more brain-damaging β-amyloid protein. In a paper published August 15 in The Journal of Neuroscience, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) found that BACE1 does more than just help produce β-amyloidit also regulates another cellular process that contributes to memory loss. This means that just inhibiting BACE1's enzymatic activity as a means to prevent or treat Alzheimer's disease isn't enoughresearchers will have to prevent cells from making it at all.

"Memory loss is a big problemnot just in Alzheimer's disease, but also in the normal aging population," said Huaxi Xu, Ph.D., professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and senior author of the study. "In this study, we wanted to better understand how BACE1 plays a role in memory loss, apart from β-amyloid production."

To do this, Xu and his team used a mouse model that produces human BACE1. Mice produce a different type of β-amyloid, one that's far less toxic than the human version. So, in this system, they could look solely at how BACE1 functions independent from β-amyloid formation. If BACE1 only acted to produce β-amyloid, the researchers would expect to see no effect when mice produce human BACE1since mouse β-amyloid isn't very toxic, extra BACE1 would be no big deal. Instead, they saw that the enzyme still impaired learning and memory, indicating a secondary function at work.

If it's not producing β-amyloid, what is BACE1 doing? Many years ago, scientist
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Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert  

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