title: [Gene diagnosis of Alzheimer's disease and Parkinson's disease].
abstract: Alzheimer's disease(AD) is the most common form of neurodegenerative diseases that causes intellectual dysfunction. AD is a genetically heterogenous disorder. Over 100 mutations have been identified in three causative genes, i.e. amyloid protein precursor(APP), presenilin 1(PS1) and presenilin 2(PS2) genes, for early-onset autosomal dominant familial AD(FAD). Apolipoprotein E(APOE) gene has been identified as susceptibility gene for late-onset FAD. The missense mutations in the causative genes lead to abnormal APP processing with overproduction of total A beta protein or A beta 42(43) isoform. The epsilon 4 allele of APOE gene is a genetic risk factor for sporadic AD as well as FAD. Parkinson's disease(PD) is another common form of neurodegenerative disease that causes movement dysfunction. Three genes, i.e. alpha-synuclein (SNCA), parkin(PARK2), and ubiquitin carboxy-terminal hydrolase L1(UCHL1) genes, have been identified as causative genes for familial PD. The B mutation of CYP2D6 gene(CYP2D6*4 allele) is a genetic risk factor for PD. Lewy body(LB), that is an intracellular inclusion body characteristic of PD, is widely distributed in the cerebral cortex of 20 to 30% of AD patients. This disease entity is called as Lewy body variant(LBV) of AD. LBV shares the genetic risk factor with AD and PD, i.e. APOE epsilon 4 allele and CYP2D6 B mutation. Gene diagnosis is possible for familial AD and PD. APOE and CYP2D6 genotyping is also applicable to the future prediction of AD and PD, respectively.
authors.affiliation: Kyoto University, Institute for Chemical Research, Uji 611-0011.
authors.forename: Seigo
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics; D008025:Ligases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D053764:Presenilin-1; D053766:Presenilin-2; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases