New genetic clue to cause of Alzheimer's Disease
Scientists have previously identified three genes, variants of which can cause early onset Alzheimer's, and one that increases risk for the late onset form. This discovery provides a completely new genetic clue about the late onset forms of AD. The researchers 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., at Mayo Clinic further confirmed the association of SORL1 variations and Alzheimer's. Researchers also 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.