DIMENSIONS Spring 2004

Spotlight on Research: Investigators Embark on New Initiative Aimed at Understanding Genetics of Late-Onset AD

by Cheryl Dawes

photo of ADRC genetics researchers

The genetic material we inherit from our parents is responsible for traits such as eye color. Research has shown that it also plays a role in whether and when we develop Alzheimer’s disease (AD). However, the relationship between our genes and this relentless memory-wasting disease is much more complex and less well understood than the relationship between our genes and the color of our eyes.

In most AD, there are probably many genes involved that interact with each other and with the environment. Although all of these interactions lead to the brain changes—plaques, tangles and neuron loss—that characterize AD, they likely take different pathways.

Untangling these multiple pathways and elucidating the genetics of AD is the goal of University of Washington ADRC researchers and other groups across the country that have embarked on a large-scale effort targeted on the most common form of AD.

For more than 15 years, UW ADRC genetics researchers Drs. Thomas Bird, Gerard Schellenberg, Ellen Wijsman and their colleagues have been investigating genetic factors involved in AD. Their identification of genes related to several forms of dementia has advanced understanding of how AD develops and extended lines of inquiry aimed at finding ways to slow or prevent its progression.

By studying families with several members who have dementia, UW researchers and other groups have identified genes responsible for three rare forms of inherited early-onset AD. The three genes are called amyloid precursor protein, presenilin 1, and presenilin 2. These genes have provided important scientific information about the biology of AD. However, mutations in these genes cause less than 2 percent of all AD in the general population. A fourth gene, apolipoprotein E, has also been identified as a risk factor for AD. However, it does not directly cause the disease. More recently, the UW team identified a mutation in the tau gene that leads to frontotemporal dementia, which is also an early-onset disease and may account for 10 percent of all dementia.

Now, in collaboration with the other ADRCs around the nation funded by the National Institute on Aging, the UW group is recruiting families to participate in a study designed to shed light on genetic factors involved in the much more common late-onset form of AD.

The study seeks to enroll 1,000 families throughout the country. The goal is to recruit 100 families from the Northwest. Eligible families must have two living siblings who have AD with onset after age 60 and a third family member over 60 who may or may not have memory loss. Blood samples are collected from each individual participating in the study. These samples, which are de-identified—marked solely as part of a particular family pedigree with a particular type of clinical history—are sent to the National Cell Repository for Alzheimer Disease (NCRAD) at Indiana University. The samples provide cell lines and genetic material for qualified researchers who are employing a variety of approaches and methods to investigate the genetics of AD.

photo of ADRC genetics staff

The national study is seeking to recruit 1000 families with AD because it has become clear that large numbers of families are required to identify multiple genes, each of which may have relatively small effects. This is an ongoing three-year study that will run through the end of 2005. The families recruited in this study are also eligible to participate in other AD research, including the other projects presently occurring at the University of Washington AD Research Center. As in most scientific projects, participants will not see direct benefit to themselves. However, the long-term goal is a better understanding of AD that will eventually lead to improved treatment or even prevention.

For more information, contact Malia Rumbaugh by phone at 206-277-6645 or toll-free 800-821-7967, or by e-mail at maliarum@u.washington.edu.

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