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 Aβ protein or Aβ42(43) isoform. The ε4 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. α-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 ε4 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.

*Kyoto University, Institute for Chemical Research, Uji 611-0011

【Key Words】Alzheimer's disease, Parkinson's disease, Gene diagnosis, amyloid, Lewy body