Genetic markers associated with late-onset Alzheimer’s

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Celera announced the publication of data from its research studies identifying several candidate genetic markers associated with late-onset Alzheimer’s disease. Two of these genes are PCK1, a gene that regulates blood glucose levels, and GALP, a gene that is modulated by insulin and regulates food intake, suggesting a link between Alzheimer’s disease and irregular glucose/insulin levels. This research paper has been accepted for publication in Human Molecular Genetics and is currently available on the publication’s website at http://hmg.oxfordjournals.org.

This is the first report of a genome-wide association study focused on testing genetic variants that are likely to change the function of a gene or protein. There were 19 single nucleotide polymorphisms (SNPs) that showed significant association with LOAD in an analysis of five independent case control sample sets, totaling 1,808 cases and 2,062 controls.

“This research study identifies genes that are likely risk factors for Alzheimer's disease, allowing us to narrow our biological focus as we strive toward an even better understanding of how these genes contribute to the development of this disease. Identifying susceptibility genes for Alzheimer's disease provides a knowledge base for the development of potential new diagnostic tests and novel therapies. These findings need to be looked at in other research samples to explore the consistency and the strength of these findings,” said Julie Williams, Ph.D., Professor of Neuropsychological Genetics at Cardiff University’s School of Medicine, and a lead author on the paper.

Celera intends to combine these markers with other previously identified markers into a Genetic Risk Score for late-onset Alzheimer’s disease that may identify individuals at elevated risk to develop the disease. Identification of individuals at elevated risk may also lead to more timely and cost-effective clinical drug trial designs. Other genetic variants that previously identified by Celera are in the death-associated protein kinase 1 (DAPK1) gene[1], in a homologue of the RPS3a gene[2], in members of the GAPD[3] (glyceraldehyde-3-phosphate dehydrogenase) gene family, and in the APPB2[4] (amyloid beta precursor protein binding family B member 2) gene. Patent applications for these Celera findings have been filed.

“This research holds promise for the development of diagnostic tests as well as new targets for drug discovery,” said Thomas White, Ph.D., Chief Scientific Officer at Celera. “As with our Genetic Risk Scores in other complex diseases such as risk of cirrhosis in hepatitis C virus infected individuals, and coronary heart disease and stroke that are currently in development, we now plan to combine these markers with others, and develop a predictive test that determines who might be at higher risk for Alzheimer’s disease.”

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