Anyone who has ever contemplated the devastating effects of a neurodegenerative disease like Alzheimer's disease has two disturbing questions embedded in the back of their mind-is it going to happen to me, and if so, when? While there is no definitive answer to the first question-unless you inherit a mutation known to cause familial AD-scientists have identified several factors, including variants of the ApoE gene, that increase one's risk of developing the disease. The question of when one may develop the disease is more difficult to answer, but a recent multicenter study led by Margaret Pericak-Vance, Duke University Medical Center, Durham, North Carolina, suggests that genetics may offer clues.

Results of the study, which appear in April's American Journal of Human Genetics currently available online, suggest a strong link between a gene on chromosome 10q and age at onset (AAO) of AD. Furthermore, the same locus also seems to link to AAO for Parkinson's disease. The authors screened almost 1,500 patients from 449 and 174 families with AD and PD members, respectively. While loci on chromosomes 4q and 8q were also highlighted by the linkage analysis, logarithm of odds (LOD) scores for these sites were not statistically significant in this analysis.

Even though the development of Alzheimer's and Parkinson's are quite different, this new data suggest there may be a common gene influencing the onset of both.—Tom Fagan

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  1. The new genome screen on Alzheimer's and Parkinson's diseases reported by Pericak-Vance et al. is a very interesting and provocative paper using age-at-onset (AAO) as a quantitative trait to search for novel AD and PD genes. The most interesting finding is that both AD and PD map to the same region of the long arm of chromosome 10. This is roughly the same region that we found earlier to be linked to AD in a paper published in Science (Bertram et al., 2000). In the same issue, Myers et al. and Ertekin-Taner et al. found evidence for linkage of AD to a more proximal region of the long arm of chromosome 10. This more proximal peak was also supported by mildly suggestive evidence for linkage published by the Duke group in two meeting reports, however, the new peak now reported by Pericak-Vance et al. in their AAO analysis corroborates the one we previously described in the more distal region of chromosome 10 (Bertam et al., 2000).

    Taken together, the authors raise the interesting possibility that there may be two AD loci on chromosome 10: a more distal 10q locus that influences age-at-onset, and a second more proximal 10q locus that influences risk. Obviously, one must be careful in discriminating between loci that confer increased risk for AD as opposed to affecting age-at-onset, since one locus could appear to affect both risk and age-at-onset (e.g., ApoE).

    It is also interesting that some risk-based AD linkage hits on other chromosomes reported by this and other groups (e.g., on chromosomes 12 and 9) do not come up positive in the new AAO-based study. This underscores the importance of continuing to carry out both types of analyses (as long as funding holds up!) Given that a number of different groups are concurrently attempting to identify novel AD genes, the real AD loci, whether for risk, AAO, or both, should eventually surface, and perhaps even be agreed upon...

    Finally, it should be said that the most intriguing aspect of the new Pericak-Vance et al. paper is that the hit on distal region of 10 not only appears to influence AAO for AD, but also for PD. This suggests that perhaps a single gene might be influencing the extent and rate of the neurodegenerative process in both diseases. However, we will not know until the gene(s) are actually identified.—Rudy Tanzi and Lars Bertram, Harvard Medical School.


    . Evidence for genetic linkage of Alzheimer's disease to chromosome 10q. Science. 2000 Dec 22;290(5500):2302-3. PubMed.

    . Susceptibility locus for Alzheimer's disease on chromosome 10. Science. 2000 Dec 22;290(5500):2304-5. PubMed.

    . Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigrees. Genet Epidemiol. 2001 Jul;21(1):19-30. PubMed.

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News Citations

  1. Insulin-Degrading Enzyme Not, After All, a Risk Factor for AD?

Further Reading

Primary Papers

  1. . Age at onset in two common neurodegenerative diseases is genetically controlled. Am J Hum Genet. 2002 Apr;70(4):985-93. PubMed.