Matsuo E S, Shin R W, Billingsley M L, Van deVoorde A, O'Connor M, Trojanowski J Q, Lee V M
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
Neuron. 1994 Oct;13(4):989-1002. doi: 10.1016/0896-6273(94)90264-x.
Tau from Alzheimer's disease (AD) paired helical filaments (PHF-tau) is phosphorylated at sites not found in autopsy-derived adult tau from normal human brains, and this suggested that PHF-tau is abnormally phosphorylated. To explore this hypothesis, we examined human adult tau from brain biopsies and demonstrated that biopsy-derived tau is phosphorylated at most sites thought to be abnormally phosphorylated in PHF-tau. These sites also were phosphorylated in autopsy-derived human fetal tau and rapidly processed rat tau. The hypophosphorylation of autopsy-derived adult human tau is due to rapid dephosphorylation postmortem, and protein phosphatases 2A (PP2A) and 2B (PP2B) in human brain biopsies dephosphorylate tau in a site-specific manner. The down-regulation of phosphatases (i.e., PP2A and PP2B) in the AD brain could lead to the generation of maximally phosphorylated PHF-tau that does not bind microtubules and aggregates as PHFs in neurofibrillary tangles and dystrophic neurites.
来自阿尔茨海默病（AD）配对螺旋丝（PHF-tau）的tau蛋白在正常人脑尸检获得的成人tau蛋白中未发现的位点发生磷酸化，这表明PHF-tau蛋白存在异常磷酸化。为了探究这一假设，我们检测了脑活检获得的人类成人tau蛋白，并证明活检获得的tau蛋白在大多数被认为在PHF-tau中异常磷酸化的位点发生了磷酸化。这些位点在尸检获得的人类胎儿tau蛋白和快速处理的大鼠tau蛋白中也发生了磷酸化。尸检获得的成人人类tau蛋白的低磷酸化是由于死后快速去磷酸化所致，人脑活检中的蛋白磷酸酶2A（PP2A）和2B（PP2B）以位点特异性方式使tau蛋白去磷酸化。AD脑中磷酸酶（即PP2A和PP2B）的下调可能导致产生最大程度磷酸化的PHF-tau蛋白，该蛋白不与微管结合，并在神经原纤维缠结和营养不良性神经突中聚集成PHF。
