Ginsberg Stephen D, Che Shaoli, Counts Scott E, Mufson Elliott J
Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA.
J Neurochem. 2006 Mar;96(5):1401-8. doi: 10.1111/j.1471-4159.2005.03641.x.
Molecular mechanisms underlying tauopathy remain undetermined. In the current study, single cell gene expression profiling was coupled with custom-designed cDNA array analysis to evaluate tau expression and other cytoskeletal elements within individual neuronal populations in patients with no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Results revealed a shift in the ratio of three-repeat tau (3Rtau) to four-repeat tau (4Rtau) mRNAs within individual human cholinergic basal forebrain (CBF) neurons within nucleus basalis (NB) and CA1 hippocampal neurons during the progression of AD, but not during normal aging. A shift in 3Rtau to 4Rtau may precipitate a cascade of events in the selective vulnerability of neurons, ultimately leading to frank neurofibrillary tangle (NFT) formation in tauopathies including AD.
tau蛋白病的分子机制仍未明确。在本研究中，单细胞基因表达谱分析与定制设计的cDNA阵列分析相结合，以评估无认知障碍（NCI）、轻度认知障碍（MCI）和阿尔茨海默病（AD）患者个体神经元群体中tau蛋白的表达及其他细胞骨架成分。结果显示，在AD进展过程中，基底核（NB）内的个体人类胆碱能基底前脑（CBF）神经元以及海马CA1神经元中，三重复tau蛋白（3Rtau）与四重复tau蛋白（4Rtau）mRNA的比例发生了变化，但在正常衰老过程中未出现这种变化。3Rtau向4Rtau的转变可能在神经元的选择性易损性中引发一系列事件，最终导致包括AD在内的tau蛋白病中出现明显的神经原纤维缠结（NFT）形成。
