• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

Celera Diagnostics Discovers Group of Genes Strongly Associated With Late-Onset Alzheimer's Disease

Posted on: Tuesday, 6 December 2005, 09:00 CST

Celera Diagnostics, a joint venture between the Applied Biosystems Group (NYSE:ABI) and Celera Genomics Group (NYSE:CRA) of Applera Corporation, today announced the publication of data showing that a novel locus on Chromosome 10 correlates strongly with increased risk for late-onset Alzheimer's disease. These findings will appear in the January 2006 edition of the American Journal of Human Genetics currently available online at: www.journals.uchicago.edu/AJHG/journal/issues/v78n1/42855/42855.html

An estimated 4.5 million Americans suffer from Alzheimer's disease and that number is expected to grow to as many as 16 million by 2050(1).

The Celera Diagnostics study evaluated more than 1,700 Alzheimer's cases and more than 1,700 age-matched controls. Results demonstrated that single nucleotide polymorphisms (SNPs) in a gene that is homologous to the RPS3A gene were associated with Alzheimer's and implicate this gene, adjacent genes, or other functional variants in the development and progression of this disease. The lead author of this paper was Andrew Grupe, Ph.D., Director of CNS Discovery Research at Celera Diagnostics, and the work was conducted in collaboration with researchers at Washington University, St. Louis, Missouri, Cardiff University in Wales, United Kingdom, the National Institute of Aging, Bethesda, Maryland, and the University of California, San Diego, California.

"This study provides valuable insights into the genetic contribution to Alzheimer's disease," said John Hardy, Ph.D., Senior Investigator, Chief, Laboratory of Neurogenetics at the National Institute on Aging, Bethesda, MD, and a co-author on the paper. "Large-scale studies with well-characterized samples from carefully selected patients allow us to discover genes that help us to identify those individuals predisposed to this debilitating disease."

The researchers chose gene-based SNPs with a preference for putative functional mutations as predicted in the Celera or public SNP databases with the aim of screening as many chromosome 10 genes as possible with at least one variant.

These findings are the latest in a series of discoveries made by Celera Diagnostics and its collaborators regarding Alzheimer's and other diseases. In the past year, Celera Diagnostics' scientists identified novel genetic variants in the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene associated with Alzheimer's(2) and also in the amyloid precursor protein binding protein B2 (APPB2)(3).

"This study is one of the first to explore the genes linked to Alzheimer's on chromosome 10, and the use of multiple sample sets with more than 3,500 samples has increased confidence in the interpretation of the data," said Thomas White, Ph.D., Chief Scientific Officer at Celera Diagnostics. "These findings, coupled with those published last year around GAPD and the APPB2 gene, provide valuable insight into the etiology of Alzheimer's and hold significant promise of enabling the development of new diagnostics and targeted therapeutics."

Study Details

A chromosome 10-specific association study was performed with 1,412 gene-based SNPs to identify susceptibility genes for Alzheimer's disease. The scan included SNPs in 677 genes out of 1,270 known or predicted genes; each gene contained one or more markers, about half of which (48%) represented putative functional mutations. In general, the initial testing was performed in a Caucasian case-control sample from the St. Louis area with 419 cases and 377 aged-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other case-control sample sets to confirm the initial association. One marker located in a gene homologous to RPS3A was significantly associated with Alzheimer's disease. RPS3A itself is a strong candidate gene for Alzheimer's disease since it has a role in regulating programmed cell death which is important in early phases of the disease. The function of the homologue is currently unknown.

About Alzheimer's disease

Alzheimer's disease, the most common form of dementia among the elderly, is a complex neurodegenerative disorder resulting from multiple genetic and nongenetic factors(4). The most common form occurs later in life and appears sporadically. However, several risk-factor genes have been implicated as causes of the disease. For example, a large body of evidence supports a central role for B-amyloid. The only well established genetic risk factor previously identified for the late-onset disease is a gene that makes one form of a protein called apolipoprotein E (APOE 4). Genetic modeling and whole genome linkage scans have implicated several genes in the genetics of sporadic Alzheimer's, but the precise genes which modulate the risk of Alzheimer's remain to be confirmed.

Advancing age is the most important known risk factor for Alzheimer's. The disease usually begins after age 60, and the number of people with the disease doubles every 5 years beyond age 65. About 5 percent of men and women ages 65 to 74 have Alzheimer's, and nearly half of those age 85 and older may have the disease. While younger people also get Alzheimer's, it is much less common.

National direct and indirect annual costs of caring for individuals with Alzheimer's are estimated to be at least $100 billion. It is estimated that Alzheimer's disease costs American business more than $61 billion a year, and of that figure, $24.6 billion covers Alzheimer health care and $36.5 billion covers costs related to caregivers of individuals with Alzheimer's, including lost productivity, absenteeism and worker replacement(5).

Celera Diagnostics' Discovery Research Approach

Celera Diagnostics compares genotype and/or gene expression profiles in samples from healthy and affected individuals to associate genetic and genomic markers with disease. To cost-effectively complete genome-wide scans, Celera Diagnostics operates an industrial-scale facility and utilizes proprietary data and know-how, including novel functional SNPs discovered by the Applera Genomics Initiative. Functional SNPs are those most likely to affect the function, amount or stability of proteins. Celera Diagnostics is currently conducting large-scale disease association studies for multiple common, complex diseases, including four forms of cardiovascular disease, breast cancer, rheumatoid arthritis, psoriasis, Alzheimer's disease, and liver disease. The pharmacogenomic studies include statin therapy and interferon responsiveness for HCV infection.

Genetic markers associated with disease may be used by Celera Diagnostics to develop new molecular diagnostic products. These products may indicate the risk or presence of disease before symptoms appear, predict the severity or expected rate of progression of a disease, or aid in monitoring response to therapy. Some of these associated markers may also be drug targets, which are being evaluated by Celera Genomics, possibly in partnership with other collaborators.

About Celera Diagnostics and Applera Corporation

Celera Diagnostics, a 50/50 joint venture between Applied Biosystems and Celera Genomics, is focused on discovery, development, and commercialization of diagnostic products. The Applied Biosystems Group (NYSE:ABI) serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA and RNA), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. Applied Biosystems' products also serve the needs of some markets outside of life science research, which we refer to as "applied markets," such as the fields of: human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, for example in food and the environment. Applied Biosystems is headquartered in Foster City, CA, and reported sales of nearly $1.8 billion during fiscal 2005. The Celera Genomics Group (NYSE:CRA) is engaged principally in the discovery and development of targeted therapeutics for cancer, autoimmune and inflammatory diseases. Celera Genomics is leveraging its proteomic, bioinformatic, and genomic capabilities to identify and validate drug targets, and to discover and develop small molecule therapeutics. It is also seeking to advance therapeutic antibody and selected small molecule drug programs in collaboration with global technology and market leaders. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.applera.com, or by telephoning 800.762.6923. Information about Applied Biosystems is available at http://www.appliedbiosystems.com/.

Forward-Looking Statements

Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe,""expect,""intend,""should," and "planned," among others. These forward-looking statements are based on Applera Corporation's current expectations. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera Corporation notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) Celera Diagnostics' unproven ability to discover, develop, or commercialize proprietary diagnostic products; (2) the uncertainty that Celera Diagnostics' products will be accepted and adopted by the market, including the risk that these products will not be competitive with products offered by other companies, or that users will not be entitled to receive adequate reimbursement for these products from third party payors such as private insurance companies and government insurance plans; (3) reliance on existing and future collaborations with other companies, including, in the case of Celera Diagnostics, its strategic alliance with Abbott Laboratories, which may not be successful; (4) uncertainty of the availability to Celera Diagnostics of intellectual property protection, limitations on their ability to protect trade secrets, the risk to them of infringement claims, and the possibility that they may need to license intellectual property from third parties to avoid or settle such claims; (5) legal, ethical, and social issues which could affect demand for Celera Diagnostics' products; and (6) other factors that might be described from time to time in Applera Corporation's filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

Copyright(C) 2005. Applera Corporation. All rights reserved. Applied Biosystems is a registered trademark and Applera, Celera, Celera Diagnostics, and Celera Genomics are trademarks of Applera Corporation or its subsidiaries in the U.S. and/or certain other countries.

Source: Business Wire

More News in this Category