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Researchers Find Region Of Chromosome 10 Linked To Risk For Alzheimer's Disease

Date:
December 22, 2000
Source:
Mayo Clinic, Jacksonville
Summary:
Researchers at Mayo Clinic in Jacksonville, Fla., have moved closer to finding a new gene that is likely to play a significant role in the development of late-onset Alzheimer's disease (LOAD). One other gene, a variant of the apolipoprotein E gene on chromosome 19, has already been identified as a risk factor for late-onset Alzheimer's, the most common form of the disease.
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JACKSONVILLE, Fla., Dec. 18, 2000 -- Researchers at Mayo Clinic in Jacksonville, Fla., have moved closer to finding a new gene that is likely to play a significant role in the development of late-onset Alzheimer's disease (LOAD). One other gene, a variant of the apolipoprotein E gene on chromosome 19, has already been identified as a risk factor for late-onset Alzheimer's, the most common form of the disease.

A Mayo Clinic team, led by Michael Hutton, Ph.D., and Steven Younkin, M.D., Ph. D., has linked LOAD to a locus on chromosome 10 that affects processing of the amyloid ß protein (Aß), a peptide important in the formation of the characteristic amyloid plaques found in the brains of people with Alzheimer's disease (AD). The group reports its findings in the Dec. 22 issue of Science.

Remarkably, LOAD was also linked to Chromosome 10 by two other research teams reporting in the same issue of Science. A consortium consisting of Alison Goate's group at The Washington University School of Medicine, John Hardy's group at Mayo Clinic in Jacksonville, and Michael Owen's team at Cardiff, Wales, searched for new LOAD genes by studying pairs of siblings where both siblings have LOAD. Their report of new results from Alison Goate's group links LOAD to the same region on chromosome 10 identified by the Hutton/Younkin team. "An important difficulty in this field has been that an apparently interesting new locus will be identified that subsequently fails to be confirmed," Younkin says. "But here, the Goate study and our study have obtained mutually confirmatory results using separate subjects and two completely different methods. That's the power of these new results."

Apart from identifying a new locus implicated as a LOAD risk factor, Hutton says the study method itself opens up a new approach to looking for AD genes. "This method has been used to study the genetics of other diseases, but it has never before applied to the genetics of LOAD," he says.

Dr. Nilufer Ertekin-Taner spearheaded the research carried out by the Hutton/Younkin team. She looked at genetic factors among 124 people in five families where the principal member was an AD patient with high blood levels of Aß42. Aß42 is a specific form of Aß that is elevated by all of the genetic mutations that cause early-onset familial AD. It is thought to be a marker for eventual development of LOAD. The team found that the level of Aß42 in the blood of family members was linked to the same small region of chromosome 10 identified in the Goate study, suggesting that the new AD susceptibility locus acts to elevate Aß42.

"Dr. Goate and the other members of her consortium are searching for the disease-associated genetic determinants that are shared by siblings who develop late-onset AD," Younkin says. "We postulated that at least some of these determinants might increase risk for AD by elevating Aß42. To find these genes we identified AD patients with a high blood level of Aß42, and we studied their families. That way we increased the chance that we would find genes that increase the risk for AD by increasing Aß42."

Younkin says the race is on to find the implicated gene. "We still have a long way to go. The next step will be to find the chromosome 10 gene and to figure out how it works," he says. "If things go as they have historically gone in this field, that will take us to new therapeutic targets." Dr. Neill Graff-Radford chairs the Department of Neurology at Mayo Clinic in Jacksonville. His patients and their families were the ones studied. Graff-Radford says when the gene is found, "depending on how frequently it does occur in the late-onset group, it's possible we may be able to identify people at risk and treat them before they get the disease."

That's the team's ultimate hope. Members say the pace of research into AD gives rise to their optimism that the gene can be found within a few years.


Story Source:

The above story is based on materials provided by Mayo Clinic, Jacksonville. Note: Materials may be edited for content and length.


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Mayo Clinic, Jacksonville. "Researchers Find Region Of Chromosome 10 Linked To Risk For Alzheimer's Disease." ScienceDaily. ScienceDaily, 22 December 2000. <www.sciencedaily.com/releases/2000/12/001222072012.htm>.
Mayo Clinic, Jacksonville. (2000, December 22). Researchers Find Region Of Chromosome 10 Linked To Risk For Alzheimer's Disease. ScienceDaily. Retrieved May 29, 2015 from www.sciencedaily.com/releases/2000/12/001222072012.htm
Mayo Clinic, Jacksonville. "Researchers Find Region Of Chromosome 10 Linked To Risk For Alzheimer's Disease." ScienceDaily. www.sciencedaily.com/releases/2000/12/001222072012.htm (accessed May 29, 2015).

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