Increase of BDNF serum concentration during donepezil treatment of patients with early Alzheimer's disease
Increase of BDNF serum concentration during donepezil treatment of patients with early Alzheimer's disease
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DOI：
10.1007/s00406-007-0764-9
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发表时间：
2008-03-01
影响因子：
4.7
通讯作者：
Laske, C.
中科院分区：
文献类型：
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作者：
Leyhe, T.;Stransky, E.;Laske, C.
阿尔茨海默病（AD）可以用乙酰胆碱酯酶（AChE）的抑制剂治疗。最近的临床前和临床研究证明乙酰胆碱酯酶抑制剂具有神经保护作用，从而具有改善疾病的潜力。这种作用的机制仍在讨论中。在动物模型中，口服AChE抑制剂导致海马和皮质中脑源性神经营养因子（BDNF）的增加。最近的研究发现，AD患者血清和脑中BDNF的减少，可能连续缺乏神经营养支持，并导致进行性神经退行性变。在基线时，通过ELISA评估了19名AD患者和20名年龄匹配的健康对照者的BDNF血清浓度，并在AD患者中进行了15个月的多奈哌齐治疗，每天10 mg（1名患者仅接受5 mg）。在用多奈哌齐治疗之前，我们发现AD患者的BDNF血清浓度（19.2 +/- 3.7 ng/ml）与健康对照组（23.2 +/- 6.0 ng/ml，P = 0.015）相比显著降低。治疗15个月后，AD患者血清BDNF浓度显著升高（23.6 ± 7.0ng/ml，P = 0.001），与健康对照组无显著差异（P = 0.882）。本研究的结果证实了先前研究的数据，即AD患者血清和脑中BDNF的下调似乎从第一次临床症状开始开始并持续。用AChE抑制剂多奈哌齐治疗伴随着AD患者中BDNF血清浓度的增加，达到健康对照的水平。因此，上调BDNF可能是乙酰胆碱酯酶抑制剂的神经保护作用的一部分。多奈哌齐的这种潜在的疾病修饰作用机制的分子机制应予以澄清。
Alzheimer's disease (AD) can be treated with inhibitors of the enzyme acetylcholinesterase (AChE). Recent pre-clinical and clinical studies gave evidence that AChE-inhibitors have neuroprotective effects and thereby a disease-modifying potential. The mechanism of this action is still discussed. In an animal model oral administration of an AChE-inhibitor lead to an increase of brain derived neurotrophic factor (BDNF) in hippocampus and cortex. Recent studies have found a decrease of BDNF in the serum and brain of AD patients with potentially consecutive lack of neurotrophic support and contribution to progressive neurodegeneration. BDNF serum concentrations were assessed by ELISA in 19 AD patients and 20 age-matched healthy controls at baseline and in the AD patients after 15 months of treatment with donepezil 10 mg per day (one patient received just 5 mg). Before treatment with donepezil we found in AD significantly decreased BDNF serum concentrations (19.2 +/- 3.7 ng/ml) as compared to healthy controls (23.2 +/- 6.0 ng/ml, P = 0.015). After 15 months of treatment the BDNF serum concentration increased significantly in the AD patients (23.6 +/- 7.0 ng/ml, P = 0.001) showing no more difference to the healthy controls (P = 0.882). The results of the present study confirm data of prior investigations that a down-regulation of BDNF in serum and brain of AD patients seems to begin with the first clinical symptoms and to be persistent. A treatment with the AChE-inhibitor donepezil is accompanied with an increase of BDNF serum concentration in AD patients reaching the level of healthy controls. Thus, up-regulation of BDNF might be part of a neuroprotective effect of AChE-inhibitors. The molecular mechanism of this potentially disease-modifying mechanism of action of donepezil should be clarified.