Identification of novel genes in late-onset Alzheimer's disease

M. A. Pericak-Vance, J. Grubber, L. R. Bailey, D. Hedges, S. West, L. Santoro, B. Kemmerer, J. L. Hall, A. M. Saunders, A. D. Roses, G. W. Small, W. K. Scott, P. M. Conneally, J. M. Vance, J. L. Haines

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

Four genes affecting Alzheimer's Disease (AD)(AP, PS1, PS2, and APOE) have been identified and a fifth potential gene localized to chromosome 12. Collectively, these genes explain at most half of the genetic effect in AD. Understanding the genetics of AD is critical to developing new treatments. The quest to find the remaining AD genes led us to undertake a large genomic screen using over 466 families (730 affected sibpairs) in late-onset AD. In conjunction with this increase in power, we initiated several novel approaches to identify potential AD-related genes. This included stratification of the data into an autopsy-confirmed subset of 199 AD families. Each of these targeted analyses resulted in the identification of novel regions containing potential AD genetic risk factors. Our most significant finding was on chromosome 9 in the autopsy-confirmed subset where we obtained an MLS of 4.31. These approaches, together with new methodologies such as conditional linkage analysis, generalized family-based association tests (PDT), and a new generation of genetic markers (SNPs), opens the door for additional AD gene discovery. Such strategies are necessary if we are to understand the subtle and complex threads that, woven together, create the intricate tapestry of AD. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)1343-1352
Number of pages10
JournalExperimental Gerontology
Volume35
Issue number9-10
DOIs
StatePublished - Dec 18 2000
Externally publishedYes

Keywords

  • Age of onset
  • Alzheimer's disease
  • Autopsy-confirmed
  • Chromosome 9
  • Genetic linkage
  • Polymorphism

ASJC Scopus subject areas

  • Aging
  • Medicine(all)

Fingerprint Dive into the research topics of 'Identification of novel genes in late-onset Alzheimer's disease'. Together they form a unique fingerprint.

  • Cite this

    Pericak-Vance, M. A., Grubber, J., Bailey, L. R., Hedges, D., West, S., Santoro, L., Kemmerer, B., Hall, J. L., Saunders, A. M., Roses, A. D., Small, G. W., Scott, W. K., Conneally, P. M., Vance, J. M., & Haines, J. L. (2000). Identification of novel genes in late-onset Alzheimer's disease. Experimental Gerontology, 35(9-10), 1343-1352. https://doi.org/10.1016/S0531-5565(00)00196-0