[Alzheimer disease: hypotheses implicating apolipoproteins E].
The most promising discovery in the study of Alzheimer's disease (AD) markers is undoubtedly the implication of apolipoprotein E (apoE). The gene of this apoliprotein is located on chromosome 19 and is characterized by three common alleles epsilon 2, epsilon 3 and epsilon 4 giving raise to 6 genotypes and 6 protein phenotypes. ApoE is well known for its role in cholesterol transport. Different studies have been performed, giving major arguments in favor of an important role of apoE in the pathophysiology of AD. These include the discovery of the relationship between the epsilon 4 allele and AD, the ability of this protein to form complexes with beta amyloid protein (A beta) in seniles plates, its presence in neurofibrillary tangles and in vessels of AD patients. Another important finding is the differential interaction between the different isoforms of apoE and tau protein. Some of the hypotheses implicate the role of different apoE isoforms on the growth and extension of neurones, perhaps by a receptor mediated pathway. It has been suggested that apoE acts as a pathological chaperone protein, or alternatively that it protects neurons by regulation of the cell membrane and modifying calcium homeostasis. It is clear that apoE genotype determination alone cannot be used for diagnosis of AD. The presence of epsilon 4 allele is only one of several risk factors for the development of the disease. Other factors may also be implicated and are the subject of ongoing research.
Blain
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Service de Médecine, CHU Nancy-Brabois, Vandoeuvre.
Merched
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Visvikis
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O'Kane
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M
Pillot
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Siest
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Jeandel
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D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism; D016875:tau Proteins / Q000378:metabolism
D000682:Amyloid; D001057:Apolipoproteins E; D016875:tau Proteins
Maladie d'Alzheimer: hypothèses impliquant les apolipoprotéines E.