Scott S A, Mufson E J, Weingartner J A, Skau K A, Crutcher K A
Department of Neurosurgery, University of Cincinnati, Ohio, USA.
J Neurosci. 1995 Sep;15(9):6213-21. doi: 10.1523/JNEUROSCI.15-09-06213.1995.
The current study analyzed NGF protein levels in the brains of patients with Alzheimer's disease (AD) as compared with aged neurologically normal individuals. An established two-site ELISA was used to measure NGF-like immunoreactivity in the hippocampus, superior temporal gyrus, superior frontal gyrus, inferior parietal lobule, frontal and occipital cortical poles, cerebellum, amygdala, putamen, and nucleus basalis of Meynert (nbM). ChAT activity was assayed in adjacent tissue samples. NGF levels were also evaluated in Parkinson's disease for comparison with both AD and age-matched control cases. Regardless of the brain bank (University of Cincinnati, Rush Presbyterian St. Luke's Medical Center in Chicago, or University of Alabama at Birmingham), NGF-like activity was at least moderately increased with AD in virtually every brain region examined except for the nbM, in which significant declines were observed. NGF levels were also increased when compared with age-matched Parkinson's cases (frontal cortex). NGF-like activity was not related to age at onset or disease duration in AD cases, nor did NGF levels correlate with age at death in the control or AD groups. Correlations between ChAT and NGF-like activity across brains varied considerably and were generally not significant. The present findings indicate that AD is characterized by a widespread increase in cortical and subcortical NGF. Although a correlation with ChAT activity was not observed in cortex, the AD-related decline in NGF found in nbM is consistent with the possibility of impaired retrograde transport of NGF to this region.
本研究分析了阿尔茨海默病（AD）患者大脑中神经生长因子（NGF）的蛋白水平，并与年龄匹配的神经功能正常个体进行比较。采用一种成熟的双位点酶联免疫吸附测定法（ELISA）来测量海马体、颞上回、额上回、顶下小叶、额叶和枕叶皮质极、小脑、杏仁核、壳核以及Meynert基底核（nbM）中NGF样免疫反应性。在相邻组织样本中检测胆碱乙酰转移酶（ChAT）活性。还评估了帕金森病患者的NGF水平，以便与AD患者及年龄匹配的对照病例进行比较。无论脑库来源如何（辛辛那提大学、芝加哥的拉什长老会圣卢克医疗中心或阿拉巴马大学伯明翰分校），除了nbM区域观察到显著下降外，在几乎每个检测的脑区中，AD患者的NGF样活性至少适度增加。与年龄匹配的帕金森病病例（额叶皮质）相比，NGF水平也有所升高。在AD病例中，NGF样活性与发病年龄或病程无关，在对照组或AD组中，NGF水平与死亡年龄也无相关性。不同大脑中ChAT与NGF样活性之间的相关性差异很大，且通常不显著。目前的研究结果表明，AD的特征是皮质和皮质下NGF广泛增加。虽然在皮质中未观察到与ChAT活性的相关性，但在nbM中发现的与AD相关的NGF下降与NGF逆向转运至该区域受损的可能性一致。
