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Scientists find new genetic clue to cause of Alzheimer's disease

group of proteins that transport APP within cells, looking for small changes, or "misspellings," in seven genes involved in moving APP within cells.

To start, the scientists combed two large data sets of genetic information from families in which more than one person has Alzheimer's disease. They were soon able to see that many of the families with Alzheimer's had variations in the SORL1 gene but not consistently in any of the other six genes.

They then expanded their search to genetic data sets from families of Northern European, Caribbean Hispanic, Caucasian, African American, and Israeli Arab heritage for changes in the SORL1 gene. Again, they found the same association between SORL1 variations and Alzheimer's disease. Searching additional data sets provided by Steven Younkin, M.D., Ph.D., of the Mayo Clinic further confirmed the association of SORL1 variations and Alzheimer's.

"We are seeing the gene implicated in multiple data sets, across ethnic and racial groups," says Farrer. He adds that the group was "encouraged and excited" by cell biology experiments that demonstrate SORL1's role in production of beta amyloid fragments.

Examining blood cells from people with and without Alzheimer's, the researchers found less than half the level of SORL1 protein in people with Alzheimer's compared to people without the disease. In laboratory experiments, they found that altering the levels of SORL1 changed the way APP was moved around in cells, with low levels of SORL1 resulting in increased production of amyloid beta fragments while high levels decreased production. However, the researchers note, other genetic and non-genetic factors are likely to affect SORL1 production in people, and more research is needed to determine the how different versions of the SORL1 gene influence production of the harmful protein fragments.


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Source:NIH/National Institute on Aging


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