Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genova, Italy.
J Alzheimers Dis. 2009;18(4):953-60. doi: 10.3233/JAD-2009-1194.
The occurrence of neuropsychiatric symptoms in patients with Alzheimer's disease hampers the clinical management and exacerbates the burden for caregivers. To what extent psychotic symptoms are genetically determined and which are the genes involved has to be established. We tested the hypothesis that the occurrence of delusions and hallucinations in AD is associated with variations in the G72/DAOA gene, which is supposed to play a key role in the glutamate pathway regulated through the NMDA receptors. A panel of single nucleotide polymorphisms were genotyped in a cohort of 185 Alzheimer's disease patients. The analysis demonstrated a nominally significant association (p< 0.05) with one single nucleotide polymorphism (rs2153674). In addition, multivariate regression showed that the rs2153674 genotype accounts for up to 15% of the variance in delusions severity, as assessed by using the Neuropsychiatric Inventory. If the results from the present study will be replicated, the glutamate hypothesis could be invoked to explain the occurrence of psychosis in neurodegenerative disorders.
阿尔茨海默病患者出现神经精神症状会妨碍临床管理，并加重照顾者的负担。需要确定精神病症状在多大程度上是由遗传决定的，以及涉及哪些基因。我们检验了这样一个假设，即 AD 患者出现妄想和幻觉与 G72/DAOA 基因的变异有关，该基因被认为在通过 NMDA 受体调节的谷氨酸途径中发挥关键作用。一组单核苷酸多态性在 185 名阿尔茨海默病患者的队列中进行了基因分型。分析显示与一个单核苷酸多态性(rs2153674)具有名义上的显著相关性(p<0.05)。此外，多元回归显示 rs2153674 基因型可解释多达 15%的神经精神病学检查评估的妄想严重程度的差异。如果本研究的结果得到复制，那么谷氨酸假说可以被援引来解释神经退行性疾病中精神病的发生。
