Evidence for genetic linkage of Alzheimer's disease to chromosome 10q.
Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Abeta, the principal component of beta-amyloid and one of the neuropathological hallmarks of Alzheimer's disease (AD). We performed parametric and nonparametric linkage analyses of seven genetic markers on chromosome 10q, six of which map near the IDE gene, in 435 multiplex AD families. These analyses revealed significant evidence of linkage for adjacent markers (D10S1671, D10S583, D10S1710, and D10S566), which was most pronounced in late-onset families. Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the IDE gene.
Bertram
L
L
Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Blacker
D
D
Mullin
K
K
Keeney
D
D
Jones
J
J
Basu
S
S
Yhu
S
S
McInnis
M G
MG
Go
R C
RC
Vekrellis
K
K
Selkoe
D J
DJ
Saunders
A J
AJ
Tanzi
R E
RE
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D015810:Linkage Disequilibrium; D008875:Middle Aged
D001057:Apolipoproteins E; D005819:Genetic Markers; D007339:Insulysin