Alzheimer disease

Alzheimer disease (AD) is the most common cause of adult-onset of progressive degenerative dementia. Dementia is a medical term used to describe a patient whose memory and/or other areas of thinking and behavior have deteriorated to the point that the individual is no longer able to function independently. An AD diagnosis is based on a history of a typical decline in cognitive abilities, usually with short-term memory loss as an early problem with the lack of evidence of other causes of dementia. In addition to a clinical diagnosis of AD, diagnosis of definite AD is made if, an age-related number of senile plaques and neurofibrillary tangles are found at the time of autopsy. Approximately 90%-95% of AD patients develop symptoms after age 60 (Late-Onset AD or LOAD). Our research focuses on the identification and evaluation of genetic risk factors for AD and the interactions of these risk factors with environmental influences.

Chromosome 12 has been of intense interest to geneticists in search of Alzheimer risk genes. A research team at the Hussman Institute for Human Genomics led by Margaret A. Pericak-Vance, Ph.D. and Vanderbilt Center for Human Genetics Research led by Jonathan L. Haines, Ph.D. performed a genome-wide association study. They have identified nine genes that may increase susceptibility for AD and confirmed a risk locus at 12q13. The locus implicated by this study is in close proximity to the vitamin D3 receptor gene. Low vitamin D levels have been reported in patients with cognitive impairment and AD. A variation in the vitamin D3 receptor gene that causes low vitamin D levels may also affect risk for AD.

For the past decade, AD genetics has been at an impasse. In the early 1990's, Dr. Pericak-Vance's discovery of the association of apolipoprotein E with AD gave hope that the genetic etiology of a host of commons diseases would unravel rapidly. Genome-wide association studies have improved researchers' ability to find disease genes of smaller or more moderate effect. Currently, Hussman Institute for Human Genomics researchers are now closely studying a number of candidate genes associated with Alzheimer risk in their data.

The identification of new AD genes may lead to a better understanding of the complex causes of AD and thus improve diagnostic tools, enhance preventative measures, and find new targets for treatment.

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