Exploring the etiology of Alzheimer disease using molecular genetics.
Alzheimer disease (AD), the most common cause of dementia in the elderly, exists in both familial and sporadic forms.
Genetic studies have led to the identification of 3 genes, bêta-amyloid precursor protein (APP), presenilin-1 (PSI), and presenilin-2 (PS2), which, when mutated, can cause familial forms of AD.
Mutations in each of these genes result in elevated levels of Abêta42/43, a proteolytic processing fragment of APP that is deposited in brains of AD patients.
Transgenic mice carrying AD-causing mutations in APP develop spontaneous age-related bêta-amyloid (Abêta) deposition and memory impairment.
Genetic linkage and association studies have also shown that the 4 allele of the apolipoprotein E (APOE) gene increases risk for AD in a dose-dependent manner in both familial and sporadic forms of AD and may account for as much as 50% of the attributable risk.
APOE genotyping may be useful both as an adjunct to diagnosis and in identifying patient groups for therapeutic intervention.
While the biological basis for the association of APOE 4 with AD is not known, age of onset and Abêta deposition are positively correlated with 4 allele dosage in some cases, suggesting that this risk may also be mediated directly or indirectly through Abêta. (...)
Mots-clés Pascal : Démence Alzheimer, Epidémiologie, Dépistage, Etiologie, Déterminisme génétique, Facteur risque, Apolipoprotéine E, Mutation, Environnement, Biologie moléculaire, Prévention, Homme, Système nerveux pathologie, Système nerveux central pathologie, Encéphale pathologie, Maladie dégénérative, Organisation santé, Economie santé, Métabolisme pathologie, Lipide, Génie biomédical
Mots-clés Pascal anglais : Alzheimer disease, Epidemiology, Medical screening, Etiology, Genetic inheritance, Risk factor, Apolipoprotein E, Mutation, Environment, Molecular biology, Prevention, Human, Nervous system diseases, Central nervous system disease, Cerebral disorder, Degenerative disease, Public health organization, Health economy, Metabolic diseases, Lipids, Biomedical engineering
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 97-0220364
Code Inist : 002B17G. Création : 21/05/1997.