Sato Noriko, Ueki Akinori, Ueno Hideo, Shinjo Hidetaka, Morita Yoshio
Department of Neuropsychiatry, Hyogo College of Medicine, Hyogo, Japan.
J Alzheimers Dis. 2009;17(2):441-8. doi: 10.3233/JAD-2009-1054.
Dopamine D3 receptor (DRD3) is present in the limbic system, which is thought to regulate affect, cognition, and activity. Thus a functional change in the DRD3 gene could in turn affect the cognitive and psychiatric symptoms of dementia of Alzheimer's type (DAT). We investigated a possible association of DRD3 genotype with DAT and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for DRD3 and apolipoprotein E (ApoE) was determined using restriction fragment length polymorphism in 210 patients with mild DAT and 224 age- and sex-matched non-demented controls. The occurrence of BPSD during the course of mild dementia was demonstrated using the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). No significant differences in DRD3 genotype were identified between DAT and controls, regardless of ApoE epsilon4. Among the DAT with BPSD, however, a significant association was observed between the presence of the DRD3 glycine allele and paranoid and delusional ideation, regardless of ApoE epsilon4. In conclusion, DRD3 gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of paranoid and delusional ideation during the course of mild DAT.
多巴胺D3受体(DRD3)存在于边缘系统中,该系统被认为可调节情感、认知和活动。因此,DRD3基因的功能变化可能会反过来影响阿尔茨海默病型痴呆(DAT)的认知和精神症状。我们研究了DRD3基因分型与DAT以及轻度DAT中痴呆的行为和心理症状(BPSD)之间的可能关联。使用限制性片段长度多态性方法,对210例轻度DAT患者和224例年龄及性别匹配的非痴呆对照者进行了DRD3和载脂蛋白E(ApoE)基因分型。采用阿尔茨海默病行为病理评分量表(BEHAVE-AD)来证实轻度痴呆过程中BPSD的发生情况。无论ApoE ε4如何,DAT患者与对照者之间未发现DRD3基因分型有显著差异。然而,在伴有BPSD的DAT患者中,无论ApoE ε4如何,DRD3甘氨酸等位基因的存在与偏执和妄想观念之间均观察到显著关联。总之,DRD3基因多态性不太可能在赋予DAT易感性方面起重要作用,但它可能参与了轻度DAT病程中偏执和妄想观念的发生。