An analysis of genetic ties to late-onset Alzheimer disease (LOAD) published in this month’s Archives of Neurology is news not so much for its actual results, but instead for the potential it represents. The results are the first to be published from the National Institute of Aging Late-Onset Alzheimer’s Disease Family Study, a coordinated effort between Alzheimer Disease Research Centers around the United States to assemble a cohort of more than 1,000 families affected by LOAD, and to make them available to all interested researchers.

The report comes from Richard Mayeux of Columbia University, New York, the coordinator of the family study, which includes investigators from 20 centers (for more information see In the work, first author Joseph Lee headed up the linkage scan of 6,000 single-nucleotide polymorphisms (SNPs) in 1,902 people from 328 families and 236 unrelated controls. The SNP coverage was not extensive, but still the study picked out markers on the ApoE gene, and in regions on chromosomes 7, 16, 17, 20, and 22 that were linked to the risk of AD.

The lab has already started a follow-on study with more subjects and better coverage, Mayeux told ARF. His group sent DNA from 5,309 members of 780 families plus 1,135 controls for genotyping of 610,000 SNPs at the Center for Inherited Disease Research at Johns Hopkins University.

Referring to the published results, Mayeux said, “The importance of this work is not that we see certain signals and locations. The important thing is that the DNA and clinical data on these families is available to anyone who is qualified and requests it.”

The late-onset family study began in 2003, after Mayeux and other researchers realized that no one research group could efficiently assemble a sample of enough families to move LOAD genetics studies forward quickly. The National Institute on Aging started a program to collaboratively identify a cohort of 1,000 families having at least two living members with late-onset disease (defined here as AD that starts after age 60), and a third member of similar age with or without disease. The NIA gave supplementary grants to AD centers around the country to start the study, and the Alzheimer’s Association pitched in to publicize the effort and help recruit families.

By now, the study has reached its goal of enrolling just over 1,000 families. Of those, the study so far has gathered complete clinical data and banked DNA and cell lines on 700. Both DNA and cells are stored at the National Cell Repository for AD at Indiana University Medical Center in Indianapolis, which also provides this service for the ADNI and DIAN consortia.

This means that if a new researcher wants to study AD genetics, he or she need not start from scratch, Mayeux told ARF. Already, the family study is facilitating new research, with 16 funded studies currently drawing on the resource.

In the same issue of the Archives of Neurology, a separate, smaller study reports on a linkage between variants in an inverted region on chromosome 17 that contains the tau gene and rare tauopathies called progressive supranuclear palsy and corticobasal dementia. These diseases can arise in the absence of known tau mutations. The present study from the lab of Kirk Wilhelmsen at the University of North Carolina in Chapel Hill performed whole genomewide association in 231 people with inherited tauopathies. It reports that specific tau gene variants could not be pinned down, but suggests that nonetheless, the tau gene is most likely to account for the association between the chromosome 17 inversion and these diseases.—Pat McCaffrey


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News Citations

  1. DIAN: Registry for eFAD to Chart Alzheimer’s Preclinical Decade

Other Citations

  1. ADNI

External Citations

  2. Center for Inherited Disease Research

Further Reading

Primary Papers

  1. . Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. Arch Neurol. 2008 Nov;65(11):1473-8. PubMed.
  2. . Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci. Arch Neurol. 2008 Nov;65(11):1518-26. PubMed.