Early-onset familial Alzheimer disease provides clues to treatment of common Alzheimer's

Nov 16 2008

The rarest kind of Alzheimer Disease (AD) - the form that transmits from parent to child with a cruel 50 percent likelihood - has been valued for its potential to shed light for the millions of people affected by the common form of AD.

Individuals who carry genetic mutations for Early-onset Familial Alzheimer Disease (eFAD) can in theory be studied and targeted for preventive treatments while they are still healthy. This has been impractical to do because these families are few and far between, comprising around one percent of all AD cases. Still, this is some 40,000 individuals out of the 4 million AD patients in the U.S. alone. Now, an international registry called Dominantly Inherited Alzheimer Network (DIAN,) is set to bridge the gap. In its path-breaking series on eFAD, the Alzforum explains the premise and promise of DIAN.

Starting in January 2009, DIAN will open its doors for adult children of eFAD families at ten participating AD research centers. These eFAD family members are invited to join a comprehensive study that aims to pave the way for future prevention trials. Volunteers can choose to be told whether they carry an eFAD genetic mutation or not; the study needs both carriers and non-carriers of the mutations.

DIAN researchers will investigate a wide range of markers-in the blood, the cerebrospinal fluid, brain images, and sensitive psychometric tests-for signs of change in the years before a person carrying an eFAD mutation actually develops symptoms of Alzheimer disease. Such markers might then be used to identify individuals who are in the preclinical stage of AD and test candidate medicines in them. The DIAN study participants themselves would also be candidates for such future treatment trials.

DIAN scientists are planning to enroll 300 people for intense observation. Funded by the National Institute of Aging and led by John C. Morris of Washington University, St. Louis, Missouri, the study will take place in 6 academic medical centers across the U.S., three centers in Australia, and one in London, UK. The participating scientists will conduct every aspect of the 6-year DIAN study in a uniform and standardized way. That way, the data from the different centers can be compared, and DIAN's pooled data can be compared to data gleaned in other big-science initiatives on the more common sporadic forms.

The Alzforum series on eFAD recounts the central role families with inherited AD played in the discovery of key genes. These discoveries bolstered the amyloid hypothesis and drove the development of new potential treatments. The series profiles many individuals and families whose lives have been shattered by eFAD and provides an in-depth explanation of the intricacies of genetic diagnosis, why eFAD patients have been excluded from clinical trials, and the potential for better diagnostics and treatments if only it were possible to reach and recruit the eFAD families who today live and suffer in isolation.

To read the full Alzforum series on Early-onset Alzheimer Disease see:  http://www.alzforum.org/eFAD/default.asp

To read the Alzforum report on DIAN see: http://www.alzforum.org/new/detail.asp?id=1939

About the Alzheimer Research Forum (http://www.alzforum.org)

The Alzheimer Research Forum, founded in 1996, is the web's most dynamic scientific community dedicated to understanding Alzheimer disease and related disorders. Access to the web site is free to all. The Forum's editorial priorities are as diverse as the needs of the research community. The web site reports on the latest scientific findings, from basic research to clinical trials; creates and maintains public databases of essential research data and reagents; and produces discussion forums to promote debate, speed the dissemination of new ideas, and break down barriers across the numerous disciplines that can contribute to the global effort to cure Alzheimer's disease.

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