Dancing in the dark?
- 90 Downloads
Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Recent estimates suggest that possibly over 70% of the genetic variance for the disease remains unaccounted for by apolipoprotein E (APOE) and the three known early-onset AD genes (APP, PSEN1, PSEN2). Specifically, one recent segregation analysis predicted the existence of up to four additional susceptibility genes having a similar or greater effect than APOE. However, most of the nearly three dozen putative AD loci proposed to date have only been inconsistently replicated in follow up analyses and more studies are necessary to distinguish false-positive findings from genuine signals. Novel AD genes will not only provide valuable clues for the development of novel therapeutic approaches, but will also allow the development of new genetic risk-rofiling strategies that are an essential prerequisite for early prediction/prevention of this devastating disease. In this review, we will present a brief overview of analytic tools in complex disease genetics, as well as a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on chromosomes 12, 10, and 9.
Index EntriesGenetics presenilin genome amyloid Alzheimer’s
Unable to display preview. Download preview PDF.
- Bertram L., Blacker D., Crystal A., et al. (2001) Candidate genes showing no evidence of association with AD: results of the NIMH-AD Genetics Initiative, in Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics (Iqbad. K., Sisodia S., and Winblad B., eds.), Chichester, U K, J. Wiley & Sons, Ltd., pp. 45–53.Google Scholar
- Fallin D., Gauntlett A. C., Scibelli P., et al. (1997) No association between the very low density lipoprotein receptor gene and late-onset Alzheimer’s disease nor interaction with the apolipoprotein E gene in population-based and clinic samples. Genet. Epidemiol. 14, 299–305.PubMedCrossRefGoogle Scholar
- NIMH Genetics Initiative AD Study Group (submitted). Results of a high resolution genome screen of 437 Alzheimer’s disease families: The NIMH Genetics Initiative.Google Scholar
- Ott J. (1999) Analysis of Human Genetic Linkage. Johns Hopkins University Press, Baltimore, MD.Google Scholar
- Roses A. D., Devlin B., Coneally P. M., et al. (1995) Measuring the genetic contribution of APOE in late-onset Alzheimer disease. Am. J. Hum. Genet. Suppl. 57, A202.Google Scholar
- Scott W. K., Grubber J., Coneally P. M., et al. (2000) Fine-mapping of the chromosome 12 Alzheimer disease locus using family-based association tests of microsatellite markers. Neurobiol. Aging 21, S129.Google Scholar