Kimura T, Ono T, Takamatsu J, Yamamoto H, Ikegami K, Kondo A, Hasegawa M, Ihara Y, Miyamoto E, Miyakawa T
Division of Clinical Research, National Kikuchi Hospital, Kumamoto, Japan.
Dementia. 1996 Jul-Aug;7(4):177-81. doi: 10.1159/000106875.
It has been reported that many tau sites in neurofibrillary tangles (NFT) are abnormally phosphorylated. We investigated the phosphorylation of tau in the hippocampus of nondemented patients and Alzheimer's disease patients by immunostaining with five site-specific antibodies against phosphorylated tau. In the pretangle stage, tau in neuropil threads was phosphorylated at serines 199, 202 and 409, numbered according to the longest human tau isoform, whereas tau in some neuronal soma was phosphorylated at serines 199, 202, 409 and 422. Tau at the stage of NFT was phosphorylated at serine 396 and threonine 231 in addition to serines 199, 202, 409 and 422. In the advanced stage, tau in ghost tangles was phosphorylated mainly at serine 396. These results suggest that the phosphorylation of each site in tau differs among the maturing stages of neurofibrillary change and that abnormal phosphorylation of tau in the neuronal soma occurs at 199, 202, 409 and 422 earlier than at threonine 231 and serine 396.
据报道，神经原纤维缠结（NFT）中的许多tau位点存在异常磷酸化。我们通过使用五种针对磷酸化tau的位点特异性抗体进行免疫染色，研究了非痴呆患者和阿尔茨海默病患者海马体中tau的磷酸化情况。在缠结前期，根据最长的人类tau异构体编号，神经毡丝中的tau在丝氨酸199、202和409处发生磷酸化，而一些神经元胞体中的tau在丝氨酸199、202、409和422处发生磷酸化。NFT阶段的tau除了在丝氨酸199、202、409和422处发生磷酸化外，还在丝氨酸396和苏氨酸231处发生磷酸化。在晚期，幽灵缠结中的tau主要在丝氨酸396处发生磷酸化。这些结果表明，tau中每个位点的磷酸化在神经原纤维变化的成熟阶段有所不同，并且神经元胞体中tau的异常磷酸化在丝氨酸199、202、409和422处比在苏氨酸231和丝氨酸396处更早发生。
