Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms
Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms
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DOI：
10.1016/j.expneurol.2005.01.026
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Ingelsson, M
中科院分区：
文献类型：
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作者：
Lee, J;Fukumoto, H;Ingelsson, M
脑源性神经营养因子（BDNF）水平在阿尔茨海默病（AD）的特定脑区域降低，BDNF基因多态性被认为影响AD风险、海马功能和记忆。我们在116例AD患者和77例对照的临床和神经病理队列中研究了BDNF 196和270位点的多态性是否与AD相关。为了确定BDNF蛋白水平与BDNF多态性和AD病理之间的关系，我们还在57例AD患者和21例对照患者中测量了颞叶关联皮层、额叶关联皮层和小脑中的BDNF。与对照组相比，阿尔茨海默病患者大脑颞叶新皮层中的BDNF蛋白水平降低了33%，而额叶和小脑皮层的水平保持不变。BDNF基因型与AD的诊断没有显著相关性，尽管在APOE ε 4等位基因携带者中BDNF 270c等位基因的比例略高。此外，BDNF蛋白水平在不同BDNF基因型和等位基因之间没有差异。神经病理学上，阿尔茨海默病患者BDNF的缺失与神经性淀粉样斑块的积累和神经元/突触标记物突触体素的缺失呈弱相关性。结果表明，所研究的BDNF多态性既不是AD中BDNF蛋白水平的强大遗传风险因素，也不是决定因素。(c) 2005爱思唯尔公司版权所有。
Levels of brain-derived neurotrophic factor (BDNF) are reduced in specific brain regions in Alzheimer's disease (AD) and BDNF gene polymorphisms have been suggested to influence AD risk, hippocampal function, and memory. We investigated whether the polymorphisms at the BDNF 196 and 270 loci were associated with AD in a clinical and neuropathological cohort of 116 AD cases and 77 control subjects. To determine how BDNF protein levels relate to BDNF polymorphisms and AD pathology, we also measured BDNF in temporal association cortex, frontal association cortex, and cerebellum in 57 of the AD and 21 control cases. BDNF protein levels in temporal neocortex of the AD brains were reduced by 33% compared to control brains, whereas levels were unchanged in frontal and cerebellar cortex. The BDNF genotypes were not significantly associated with a diagnosis of AD, although the BDNF 270 C allele was slightly overrepresented among carriers of the APOE epsilon 4 allele. Moreover, BDNF protein levels did not differ between the various BDNF genotypes and alleles. Neuropathologically, the loss of BDNF in AD showed a weak correlation with accumulation of neuritic amyloid plaques and loss of the neuronal/synaptic marker synaptophysin. The results suggest that the investigated BDNF polymorphisms are neither robust genetic risk factors nor determinants of BDNF protein levels in AD. (c) 2005 Elsevier Inc. All rights reserved.