Chuu Jenny Y-J, Taylor Joy L, Tinklenberg Jared, Noda Art, Yesavage Jerome, Murphy Greer M
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5485, and the VA Sierra Pacific Mental Illness Research Education and Clinical Center, Palo Alto, CA, USA.
J Alzheimers Dis. 2006 Mar;9(1):43-9. doi: 10.3233/jad-2006-9104.
It is largely unknown why some patients with Alzheimer's disease (AD) decline cognitively more rapidly than others. Genetic differences among patients could influence rate of decline. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in the survival neurons and in memory function. BDNF levels are reduced in the brain in AD. The Val66Met polymorphism in the BDNF gene modifies neuronal BDNF secretion, and affects hippocampal function and memory performance. We tested the hypothesis that the BDNF Val66Met polymorphism influences rate of cognitive decline in AD. In a sample of 149 AD patients followed for an average of 3.9 years, we found no effect of BDNF Val66Met genotype on rate of change in the Mini Mental State Examination. Results were similar when we excluded patients taking an acetylcholinesterase inhibitor, those placed in a nursing home during the study, or those with a neuropathological diagnosis that included AD plus an entity other than AD. We also found no evidence that the effects of the BDNF Val66Met genotype depend on APOE genotype, which itself had no effect on rate of cognitive change. These findings suggest that the functional BDNF Val66Met variant is not a major determinant of rate of cognitive decline in AD.
目前尚不清楚为何有些阿尔茨海默病（AD）患者的认知能力衰退速度比其他患者更快。患者之间的基因差异可能会影响衰退速度。脑源性神经营养因子（BDNF）是一种对神经元存活和记忆功能很重要的神经营养蛋白。在AD患者的大脑中，BDNF水平会降低。BDNF基因中的Val66Met多态性会改变神经元BDNF的分泌，并影响海马体功能和记忆表现。我们检验了BDNF Val66Met多态性会影响AD患者认知衰退速度这一假设。在一个由149名AD患者组成的样本中，这些患者平均被随访了3.9年，我们发现BDNF Val66Met基因型对简易精神状态检查表的变化率没有影响。当我们排除服用乙酰胆碱酯酶抑制剂的患者、在研究期间被安置在养老院的患者或那些有包括AD加AD以外其他病症的神经病理学诊断的患者时，结果相似。我们也没有发现证据表明BDNF Val66Met基因型的影响取决于APOE基因型，而APOE基因型本身对认知变化率没有影响。这些发现表明，功能性BDNF Val66Met变体不是AD患者认知衰退速度的主要决定因素。
