title: [Familial forms of Alzheimer's disease].
abstract: TWO SITUATIONS: Familial occurrence of Alzheimer disease is observed in two quite different situations. The more common is the familial aggregation caused by the Apo E4 genotype. Nevertheless, APO E4 as a major risk factor is neither sufficient nor necessary to induce Alzheimer disease. The second possibility are the autosomal dominant forms of Alzheimer disease. Three different genes are concerned. MUTATIONS: The more frequent mutations are found in the Presenilin 1 gene (PS1), mutations in the amyloid precursor protein (APP) are rare and only a few Presenilin 2 gene (PS2) mutations are reported.
  The main clinical characteristic of these autosomal dominant forms is an early age of onset below 60. Neuropathology is similar to sporadic cases: senile plaques with A beta peptide as a major component and neurofibrillary tangles containing Tau protein.
  
  
  RESULTS
  The demonstration that both APP, PS1, and PS2 gene mutations enhance the processing of APP to form A beta peptide is a major argument supporting the amyloid hypothesis of Alzheimer disease. This better knowledge of APP and PS1,2 processing and their interactions with binding proteins does permit to develop treatment strategies.
authors.affiliation: Département de neurologie, CHU, INSERM EMI 9906, IFRMP, Faculté de Médecine et de Pharmacie, Rouen.
authors.forename: Lucie
authors.initials: L
authors.lastname: Maréchal
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D004195:Disease Models, Animal; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D053764:Presenilin-1; D053766:Presenilin-2; D012307:Risk Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2