Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease
Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease
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DOI：
10.1111/j.1471-4159.2005.03641.x
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发表时间：
2006-03-01
影响因子：
4.7
通讯作者：
Mufson, EJ
中科院分区：
文献类型：
--
作者：
Ginsberg, SD;Che, S;Mufson, EJ
tau蛋白病的分子机制仍未确定。在当前的研究中，单细胞基因表达谱与定制设计的 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) 患者个体神经元群内 tau 表达和其他细胞骨架元件。结果显示，在 AD 进展过程中，基底核 (NB) 内的个体胆碱能基底前脑 (CBF) 神经元和海马 CA1 神经元内的三重复 tau (3Rtau) 与四重复 tau (4Rtau) mRNA 的比率发生了变化，但在正常衰老过程中没有变化。 3Rtau 向 4Rtau 的转变可能会引发神经元选择性脆弱性中的一系列事件，最终导致包括 AD 在内的 tau 病中明显的神经原纤维缠结 (NFT) 形成。
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.