Study identifies novel genes associated with Alzeimer's

Scientists from US company Celera in collaboration with Cardiff University in Wales have identified several candidate genetic markers associated with late-onset Alzheimer's disease.

The candidates include markers in multiple genes that have never been associated with late-onset Alzheimer's. 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.

The research paper has been accepted for publication in Human Molecular Genetics.

This is the first report of a genome-wide association study in Alzheimer's 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 Alzheimer's in an analysis of five independent case control sample sets, totaling 1808 cases and 2062 controls.

Three of the identified markers were located close to the APOE gene, a known risk factor for Alzheimer's. An additional 16 markers mapped to biological candidate genes, such as PCK1 and GALP, to chromosome segments that are considered to harbour genetic mutations that lead to a higher risk for Alzheimer's, or to novel genes.

"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," Professor Julie Williams of Cardiff University's School of Medicine said.. "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."

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 correlate strongly with Alzheimer's previously identified by Celera are in the death-associated protein kinase 1 (DAPK1) gene, in a homologue of the RPS3a gene, in members of the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene family, and in the APPB2 (amyloid beta precursor protein binding family B member 2) gene. Several of these previously reported markers play a role in programmed cell death, supporting this as one of the underlying disease mechanisms of Alzheimer's. 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," Celera's chief scientific officer Dr Thomas White said. "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."

Source: Celera