ヒト Germline 遺伝子検査の現状と今後の課題

神経変性疾患の遺伝子診断：
アルツハイマー病・パーキンソン病の原因遺伝子について

田　中　静　吾*
　　　　　　　　　　　　　　　　　　　　　　
Gene Diagnosis of Alzheimer's Disease and Parkinson's Disease
Seigo TANAKA, MD*

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.
[Rinsho Byori 50 : 965〜969, 2002]

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

【Key Words】Alzheimer's disease(アルツハイマー病)，Parkinson's disease(パーキンソン病)，Gene diagnosis(遺伝子診断)，amyloid(アミロイド)，Lewy body(レビー小体)，

*京都大学化学研究所生体反応設計研究部門III(〒611-0011 宇治市五ヶ庄)

E-mail :seigo@scl.kyoto-u.ac.jp