Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10q-Reference-Cited by-同舟云学术

Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10q

Published:2000-12-22 Issue:5500 Volume:290 Page:2302-2303
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Bertram Lars¹,Blacker Deborah²³,Mullin Kristina¹,Keeney Devon¹,Jones Jennifer¹,Basu Sanjay¹,Yhu Stephen¹,McInnis Melvin G.⁴,Go Rodney C. P.⁵,Vekrellis Konstantinos⁶,Selkoe Dennis J.⁶,Saunders Aleister J.¹,Tanzi Rudolph E.¹

Affiliation:

1. Genetics and Aging Unit, Department of Neurology,

2. Gerontology Research Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

3. Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.

4. Department of Psychiatry, Johns Hopkins University Medical Institutions, Baltimore, MD 21287, USA.

5. Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL 35294, USA.

6. Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Abstract

Recent studies suggest that insulin-degrading enzyme (IDE) in neurons and microglia degrades Aβ, the principal component of β-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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference21 articles.

1. Neurons Regulate Extracellular Levels of Amyloid β-Protein via Proteolysis by Insulin-Degrading Enzyme

2. Subjects were collected as part of the NIMH Genetics Initiative following a standardized protocol applying NINCDS/ADRDA (National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) criteria for the diagnosis of AD (3). Only families in which all sampled affected individuals had onset ages ≥50 years were included ( n = 435 families n = 1426 subjects mean age of onset = 72.5 ± 7.7 years range 50 to 97 years). Additional information on the procedures is available as supplemental material (12).

3. Blacker D., et al., Neurology 48, 139 (1997).

4. Kehoe P., et al., Hum. Mol. Genet. 8, 237 (1999).

5. A. J. Myers et al. Neurobiol. Aging 21 (suppl.) S103 (2000).

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