[Familial forms of Alzheimer's disease].
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.
Maréchal
Lucie
L
Département de neurologie, CHU, INSERM EMI 9906, IFRMP, Faculté de Médecine et de Pharmacie, Rouen.
Campion
Dominique
D
Hannequin
Didier
D
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
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