Genetic and molecular advances in Alzheimer's disease.
The abnormal deposition of amyloid beta protein (A beta) in the brain is the major neuropathological characteristic of Alzheimer's disease (AD). The disease in some early-onset familial cases develops as a result of mutations in the gene coding for the beta-amyloid precursor protein (beta APP) and in the majority of the rest appears to be caused by an unidentified gene on chromosome 14. Only one of the beta APP gene mutations has been associated with aberrant beta APP processing, resulting in an excess production of A beta in vitro, a result suggesting that there might be excessive A beta cleavage from beta APP in AD in vivo. By contrast with the beta APP mutants, no particular allele of the apolipoprotein E (APOE) gene predicts the disease completely but one allele is associated with the disease suggesting APOE is a risk locus for AD. This discovery has been linked to increased deposition of A beta in those cases carrying the risk allele. However, the genetic evidence is currently not sufficient to indicate whether beta APP mismetabolism, direct or indirect A beta neurotoxicity or dysfunction of beta APP (or its derivatives) are central to the AD process.
Mullan
M
M
Dept of Psychiatry, University of South Florida, Tampa 33613.
Crawford
F
F
D017668:Age of Onset; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002888:Chromosomes, Human, Pair 19; D005796:Genes; D008040:Genetic Linkage; D005823:Genetics / Q000639:trends; D006801:Humans; D008967:Molecular Biology / Q000639:trends; D009154:Mutation; D009498:Neurotoxins
D016564:Amyloid beta-Protein Precursor; D009498:Neurotoxins