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Alzheimer’s disease risk increases with maternal inheritance

Philadelphia, PA, 15 November 2010 - A family history of Alzheimer’s disease significantly increases the risk for developing this disorder, but a new study in Biological Psychiatry suggests that which of your parents has the disease is very important.

Alzheimer’s is the most common form of dementia in late-life, affecting over 5 million elderly in the United States alone. In order to develop preventative treatments, it is necessary to identify those individuals who are at highest risk for developing Alzheimer’s.

Although individuals with a parental history of Alzheimer’s are at increased risk for developing the disease, the specific biological and genetic mechanisms accounting for this increased risk are not known.

An important consideration may be a phenomenon called genomic imprinting, where the pattern of the inherited disease differs based on whether the risk genes are inherited from the mother or the father. Imprinting is a type of epigenetic regulation, meaning that long lasting changes in gene function are produced through regulatory mechanisms rather than by altering the sequence of the DNA.

In this new study, researchers set out to evaluate Alzheimer’s risk in healthy, cognitively normal individuals by measuring their cerebrospinal fluid proteins, which are known to be altered in Alzheimer’s. They compared individuals with a maternal or paternal history of Alzheimer’s to individuals with no family history.

Only individuals whose mothers had Alzheimer’s showed altered levels of a protein called amyloid, a major hallmark of Alzheimer’s pathology, as well as proteins involved with oxidative stress (i.e., free radicals, which are harmful to the brain as well as the rest of the body). In contrast, individuals whose fathers had Alzheimer’s and those with no family history had protein levels within normal range.

“Our data indicate that adult children of mothers with Alzheimer’s may be at increased risk for developing the disease,” explained Dr. Lisa Mosconi, the first author on the study. “It is therefore extremely important to understand the genetic mechanisms involved in maternal transmission of Alzheimer’s disease, which are currently unknown. Identifying a genetic predictor for the disease might lead to preventive treatments years before the onset of clinical symptoms.”

Dr. John Krystal, Editor of Biological Psychiatry, added: “This study is very important because we are just beginning to understand the epigenetic control of particular genes. In theory, some day, one might develop a medication that reduces the risks associated with a maternal history of Alzheimer’s disease.”

The authors cautioned that additional follow-up research is now needed to test the usefulness of these protein measures for predictive purposes and to investigate potential susceptibility genes for Alzheimer’s disease.

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Notes to Editors:
The article is “Oxidative Stress and Amyloid-Beta Pathology in Normal Individuals with A Maternal History of Alzheimer's” by Lisa Mosconi, Lidia Glodzik, Rachel Mistur, Pauline McHugh, Kenneth E. Rich, Elizabeth Javier, Schantel Williams, Elizabeth Pirraglia, Susan De Santi, Pankaj D. Mehta, Raymond Zinkowski, Kaj Blennow, Domenico Pratico, and Mony J. de Leon. Mosconi, Glodzik, Mistur, McHugh, Rich, Javier, Williams, Pirraglia, De Santi, and de Leon are affiliated with New York University School of Medicine, New York, New York. de Leon is also with Nathan Kline Institute, Orangeburg, New York. De Santi is also with Bayer HealthCare Pharmaceuticals Inc., Montville, New Jersey. Mehta is from the Institute for Basic Research, Staten Island, New York. Zinkowski is affiliated with Applied Neurosolutions, Vernon Hills, Illinois. Blennow is from University of Göteborg, Sahlgrenska University Hospital, Gothenburg, Sweden. Pratico is with Temple University School of Medicine, Philadelphia, Pennsylvania. The article appears in Biological Psychiatry, Volume 68, Issue 10 (November 15, 2010), published by Elsevier.

The authors’ disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological-Psychiatry-Editorial-Disclosures-7-22-10.pdf.

Full text of the article mentioned above is available upon request. Contact Chris J. Pfister at c.pfister@elsevier.com to obtain a copy or to schedule an interview

About Biological Psychiatry
This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

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