Division of Molecular Medicine, Rudjer Boskovic Institute, Croatia.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):356-62. doi: 10.1016/j.pnpbp.2010.10.020. Epub 2010 Oct 31.
Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder with a high prevalence. Since behavioral disturbances, such as psychotic symptoms, represent a key feature of AD, genes related to dopamine, serotonin and brain derived neurotrophic factor (BDNF), are considered as candidate genes for AD. BDNF is a neurotrophin that regulates neurodevelopment, neuroplasticity, and neuronal functions. BDNF is involved in the etiopathogenesis of psychiatric and neurodegenerative disorders. A single base pair polymorphism (BDNF Val66Met) was reported to be associated with AD and/or schizophrenia, as well as other psychoses, although some studies failed to replicate these findings. The aim of the study was to evaluate the association between BDNF Val66Met variants and AD, as well as onset of AD or presence of psychotic symptoms in AD.
BDNF Val66Met was analyzed in 211 patients with AD and in 402 aged healthy control subjects. All subjects were ethnically homogenous Caucasians from Croatia, and were subdivided according to the gender, onset of AD, and presence of psychotic symptoms. A χ(2) test, with Bonferroni correction and standardized residuals were used to evaluate the data.
Distribution of the BDNF Val66Met genotypes differed significantly between male and female AD patients with or without psychotic symptoms. This difference was due to the significant contribution of the Met/Val genotype and the combined Met/Met and Met/Val genotypes between psychotic and non-psychotic symptoms in male, but not in female patients with AD. The frequency of the gene variants of the BDNF Val66Met did not differ significantly among male and female patients with AD and control subjects, or between male and female patients with early or late onset AD. There were significant sex related differences in age, duration of illness and scores of dementia between patients with AD.
Our male patients were younger, had shorter duration of illness, and had less severe dementia and higher cognitive performance than female AD patients. The gene variants of the BDNF Val66Met polymorphism were significantly associated with the presence of psychotic symptoms in male, but not in female patients with AD. The results had adequate statistical power to suggest that BDNF Val66Met was not related to susceptibility to AD or the onset of AD, but that presence of one or two Met alleles of BDNF Val66Met polymorphism might present a risk factor for psychosis in AD.
阿尔茨海默病（AD）是一种不可逆转的、进行性的神经退行性疾病，其患病率较高。由于行为障碍，如精神病症状，是 AD 的一个关键特征，因此与多巴胺、血清素和脑源性神经营养因子（BDNF）相关的基因被认为是 AD 的候选基因。BDNF 是一种神经营养因子，可调节神经发育、神经可塑性和神经元功能。BDNF 参与了精神疾病和神经退行性疾病的发病机制。据报道，单一碱基对多态性（BDNF Val66Met）与 AD 以及精神分裂症和其他精神病有关，尽管一些研究未能复制这些发现。本研究旨在评估 BDNF Val66Met 变体与 AD 以及 AD 发病或出现精神病症状之间的关联。
在 211 名 AD 患者和 402 名年龄匹配的健康对照者中分析了 BDNF Val66Met。所有受试者均为来自克罗地亚的同种族白人，根据性别、AD 发病和精神病症状的存在进行了细分。采用卡方检验（ χ 2 检验），并进行了 Bonferroni 校正和标准化残差分析。
BDNF Val66Met 基因型在有或无精神病症状的男性和女性 AD 患者之间的分布有显著差异。这种差异是由于在男性 AD 患者中，Met/Val 基因型以及 Met/Met 和 Met/Val 复合基因型在精神病和非精神病症状之间的显著贡献所致，但在女性 AD 患者中并非如此。BDNF Val66Met 基因变异在 AD 患者和对照组的男性和女性、早期或晚期发病的 AD 患者之间的频率无显著差异。AD 患者的年龄、病程和痴呆评分存在显著的性别相关差异。
我们的男性患者比女性患者年龄更小、病程更短、痴呆程度更轻、认知功能更高。BDNF Val66Met 多态性的基因变异与男性 AD 患者的精神病症状存在显著相关，但与女性 AD 患者无关。研究结果具有足够的统计效力，表明 BDNF Val66Met 与 AD 的易感性或发病无关，但 BDNF Val66Met 多态性的一个或两个 Met 等位基因可能是 AD 中精神病的危险因素。
