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Alzheimer's gene identified

An international effort led by scientists at the University of Toronto, Columbia University and Boston University has isolated another gene responsible for Alzheimer's disease.

The discovery, outlined in the Jan. 14 advance on-line edition of Nature Genetics (February print edition), shows how a team of researchers analyzed the faulty processing of the amyloid precursor protein (APP) long associated with Alzheimer's disease and linked it to a new gene (SORL1). The five-year study included multiple centres such as Columbia University, Boston University and the Mayo Clinic and tested over 6,000 DNA samples from Caucasians, Hispanics, Israeli-Arabs and African Americans and uncovered two consistent patterns that linked the SORL1 gene to people afflicted with Alzheimer's.

"Instead of scanning all the genes in the entire genome, we had an idea of what an Alzheimer's disease-causing gene would look like based on past discoveries," says senior author University Professor Peter St. George-Hyslop, director of the Centre for Research in Neurodegenerative Diseases (CRND) at the University of Toronto. "We knew that the abnormalities in APP processing and the accumulation of its toxic amyloid beta (A) peptide derivative cause Alzheimer's, so we hypothesized that other genes associated with APP regulation might also cause the disease."

SORL1 governs the distribution of APP inside nerve cells of the brain. When working properly, the SORL1 protein regulates APP by diverting it into specific certain regions of the cell. When the level of the SORL1 gene is reduced, APP accumulates in a different region of the cell, where it is degraded into Abeta fragments abnormal protein fragments which then cause Alzheimer's disease.

"We discovered two different variants in the SORL1 gene that are associated with increased risk of AD in different ethnic groups, says Dr. Ekaterina Rogaeva, first author of the study and also part of CRND. "This em
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Contact: Karen Kelly
k.kelly@utoronto.ca
416-978-5949
University of Toronto
14-Jan-2007


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