11 January 2001. Three independent studies published in the 22 December issue
of Science reported that chromosome 10 probably harbors one or more genes that
confer an increased susceptibility to late-onset Alzheimer's disease. The specific
gene or genes have not yet been identified, but the fact that three separate studies
employing different methods and datasets make it more likely that the linkage
is not an experimental artifact.
A team led by Alison Goate at Washington University, St Louis, screened the
entire genome of over 430 sibling pairs with Alzheimer's and identified a susceptibility
locus on chromosome 10. "Two things about this new risk factor seem very significant,"
says Goate. "First, it appears to have as big an effect on risk as ApoE4 in
our sample. Secondly, it has that effect independent of ApoE4," the only gene
so far confirmed to be a risk factor for late-onset AD. A second paper by Steven
Younkin and colleagues at Mayo Clinic, Jacksonville, Florida, mapped a gene that modifies
plasma concentrations of Aβ-peptide to exactly the same region of chromosome
10. Plasma Aβ levels are altered in inherited forms of early-onset AD. In
the third Science paper, Rudolph Tanzi and colleagues at Massachusetts General
Hospital report a linkage also to chromosome 10, albeit not to the same exact
locus. "The region Tanzi's group identified is not in exactly the same place
as the other two studies, but the linkage approach does not give precise localisation
so we could be detecting the effects of the same gene", says Goate. The Tanzi
group focused on chromosome 10 because it contains the gene for insulin degrading
enzyme (IDE), a protein that is thought to degrade β-amyloid in the brain,
and is considered a candidate gene for a risk factor for AD.-Hakon Heimer.
Reference:Myers A et al. Susceptibility locus for Alzheimer's disease on chromosome 10. Science 2000 Dec 22;290(5500):2304-5. Abstract.
Ertekin-Taner N, Graff-Radford N, Younkin LH, Eckman C, Baker M, Adamson J, Ronald J, Blangero J, Hutton M, Younkin SG. Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees. Science. 2000 Dec 22;290(5500):2303-4. Abstract
Bertram L, Blacker D, Mullin K, Keeney D, Jones J, Basu S, Yhu S, McInnis MG, Go RC, Vekrellis K, Selkoe DJ, Saunders AJ, Tanzi RE. Evidence for genetic linkage of Alzheimer's disease to chromosome 10q. Science. 2000 Dec 22;290(5500):2302-3. Abstract