{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:47:30Z","timestamp":1780354050345,"version":"3.54.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[1996,8,1]],"date-time":"1996-08-01T00:00:00Z","timestamp":838857600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[1996,8]]},"DOI":"10.1038\/nm0896-871","type":"journal-article","created":{"date-parts":[[2004,8,19]],"date-time":"2004-08-19T01:39:14Z","timestamp":1092879554000},"page":"871-875","source":"Crossref","is-referenced-by-count":277,"title":["Glycosylation of microtubule\u2013associated protein tau: An abnormal posttranslational modification in Alzheimer's disease"],"prefix":"10.1038","volume":"2","author":[{"given":"Jian-Zhi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Grundke-Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"BFnm0896871_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0304-3940(86)90288-0","volume":"65","author":"H Braak","year":"1986","unstructured":"Braak, H., Braak, E., Grundke-Iqbal, I. & Iqbal, K. Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: A third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci. Lett. 65, 351\u2013355 (1986).","journal-title":"Neurosci. Lett."},{"key":"BFnm0896871_CR2","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/0022-510X(70)90063-8","volume":"11","author":"BE Tomlinson","year":"1970","unstructured":"Tomlinson, B.E., Blessed, G. & Roth, M. Observations on the brains of demented old people. J. Neurol. Sci. 11, 205\u2013242 (1970).","journal-title":"J. Neurol. Sci."},{"key":"BFnm0896871_CR3","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/BF00688184","volume":"74","author":"I Alafuzoff","year":"1987","unstructured":"Alafuzoff, I., Iqbal, K., Friden, H., Adolfsson, R. & Winblad, B. Histopathological criteria for progressive dementia disorders: Clinical-pathological correlation and classification by multivariate data analysis. Acta Neuropathol. (Berl.) 74, 209\u2013225 (1987).","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"BFnm0896871_CR4","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1016\/S0021-9258(17)38495-8","volume":"261","author":"I Grundke-Iqbal","year":"1986","unstructured":"Grundke-Iqbal, I. et al. Microtubule-associated protein tau: A component of Alzheimer paired helical filaments. J. Biol Chem. 261, 6084\u20136089 (1986).","journal-title":"J. Biol Chem."},{"key":"BFnm0896871_CR5","doi-asserted-by":"publisher","first-page":"4913","DOI":"10.1073\/pnas.83.13.4913","volume":"83","author":"I Grundke-Iqbal","year":"1986","unstructured":"Grundke-Iqbal, I. et al. Abnormal phosphorylation of the microtubule-associated protein \u03c4 (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA 83, 4913\u20134917 (1986).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm0896871_CR6","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/S0140-6736(86)92134-3","volume":"2","author":"K Iqbal","year":"1986","unstructured":"Iqbal, K. et al. Defective brain microtubule assembly in Alzheimer's disease. Lancet 2, 421\u2013426 (1986).","journal-title":"Lancet"},{"key":"BFnm0896871_CR7","doi-asserted-by":"crossref","first-page":"24374","DOI":"10.1016\/S0021-9258(20)80536-5","volume":"268","author":"E K\u00f6pke","year":"1993","unstructured":"K\u00f6pke, E. et al. Microbutule associated protein tau: Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. J. Biol. Chem. 268, 24374\u201324384 (1993).","journal-title":"J. Biol. Chem."},{"key":"BFnm0896871_CR8","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1083\/jcb.103.6.2739","volume":"103","author":"DG Drubin","year":"1986","unstructured":"Drubin, D.G. & Kirschner, M.W. Tau protein function in living cells. J. Cell Biol. 103, 2739\u201346 (1986).","journal-title":"J. Cell Biol."},{"key":"BFnm0896871_CR9","doi-asserted-by":"crossref","first-page":"22019","DOI":"10.1016\/S0021-9258(18)54739-6","volume":"266","author":"GC Ruben","year":"1991","unstructured":"Ruben, G.C. et al. The microtubule associated protein tau forms a triple-stranded left-hand helical polymer. J. Biol. Chem. 266, 22019\u201322027 (1991).","journal-title":"J. Biol. Chem."},{"key":"BFnm0896871_CR10","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0014-5793(95)00486-S","volume":"366","author":"WJ Goux","year":"1995","unstructured":"Goux, W.J., Rodriguez, S. & Sparkman, D.R. Analysis of the core components of Alzheimer paired helical filaments: A gas chromatography\/mass spectrometry characterization of fatty acids, carbohydrates and long-chain bases. FEBS Lett. 366, 81\u201385 (1995).","journal-title":"FEBS Lett."},{"key":"BFnm0896871_CR11","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/0006-8993(92)91092-S","volume":"590","author":"GC Ruben","year":"1992","unstructured":"Ruben, G.C., Iqbal, K., Wisniewski, H.M., Johnson, J.E., Jr., & Grundke-Iqbal, I. Alzheimer neurofibrillary tangles contain 2.1 nm filaments structurally identical to the microtubule associated protein tau: A high resolution transmission electron microscope study of tangles and senile plaque core amyloid. Brain Res. 590, 164\u2013179 (1992).","journal-title":"Brain Res."},{"key":"BFnm0896871_CR12","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nm0796-783","volume":"2","author":"A Alonso","year":"1996","unstructured":"Alonso, A., del, C., Grundke-Iqbal, I. & Iqbal, K. Alzheimer disease hyperphos-phorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nature Med. 2, 783\u2013787 (1996).","journal-title":"Nature Med."},{"key":"BFnm0896871_CR13","doi-asserted-by":"publisher","first-page":"4854","DOI":"10.1074\/jbc.270.9.4854","volume":"270","author":"J-Z Wang","year":"1995","unstructured":"Wang, J.-Z., Gong, C.-X., Zaidi, T., Grundke-Iqbal, I. & Iqbal, K. Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. J. Biol. Chem. 270, 4854\u20134860 (1995).","journal-title":"J. Biol. Chem."},{"issue":"12","key":"BFnm0896871_CR14","doi-asserted-by":"publisher","first-page":"5710","DOI":"10.1073\/pnas.91.12.5710","volume":"91","author":"M. A. Smith","year":"1994","unstructured":"Smith, M.A. et al. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc. Natl. Acad. Sci. USA 91, 5710 (1994).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"BFnm0896871_CR15","doi-asserted-by":"crossref","first-page":"21614","DOI":"10.1016\/S0021-9258(17)31849-5","volume":"269","author":"MD Ledesma","year":"1994","unstructured":"Ledesma, M.D., Bonay, P., Colaco, C. & Avila, J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J. Biol. Chem. 269, 21614\u201321619 (1994).","journal-title":"J. Biol. Chem."},{"issue":"16","key":"BFnm0896871_CR16","doi-asserted-by":"publisher","first-page":"7787","DOI":"10.1073\/pnas.91.16.7787","volume":"91","author":"S. D. Yan","year":"1994","unstructured":"Yan, S.D. et al. Glycated tau protein in Alzheimer disease: A mechanism for induction of oxidant stress. Proc. Natl. Acad. Sci. USA 91, 7787 (1994).","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"4","key":"BFnm0896871_CR17","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1046\/j.1471-4159.1995.65041658.x","volume":"65","author":"M. Dolores Ledesma","year":"2002","unstructured":"Ledesma, M.D., Bonay, P. & Avila, J. \u03c4 Protein from Alzheimer's disease patients is glycated at its tubulin-binding domain. J. Neurochem. 65, 1658 (1995).","journal-title":"Journal of Neurochemistry"},{"key":"BFnm0896871_CR18","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/0022-2836(88)90015-0","volume":"203","author":"S Tanaka","year":"1988","unstructured":"Tanaka, S., Avigad, G., Brodsky, B. & Eikenberry, E.F. Glycation induces expansion of molecular packing of collagen. J. Mol Biol. 203, 495\u2013505 (1988).","journal-title":"J. Mol Biol."},{"key":"BFnm0896871_CR19","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/0006-8993(89)91396-6","volume":"477","author":"C Bancher","year":"1989","unstructured":"Bancher, C. et al. Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res. 477, 90\u201399 (1989).","journal-title":"Brain Res."},{"key":"BFnm0896871_CR20","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/nm0795-693","volume":"1","author":"SD Yan","year":"1995","unstructured":"Yan, S.D. et al. Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid \u03b2-peptide. Nature Med. 1, 693\u2013699 (1995).","journal-title":"Nature Med."},{"key":"BFnm0896871_CR21","first-page":"375","volume":"60","author":"Sch Papasozomenos","year":"1989","unstructured":"Papasozomenos, S.ch. Tau protein immunoreactivity in dementia of the Alzheimer type. II. Electron microscopy and pathogenetic implications: Effects of fixation on the morphology of the Alzheimer's abnormal filaments. Lab. Invest. 60, 375\u2013389 (1989).","journal-title":"Lab. Invest."},{"key":"BFnm0896871_CR22","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1083\/jcb.131.5.1327","volume":"131","author":"R Brandt","year":"1995","unstructured":"Brandt, R., L\u00e9ger, J. & Lee, G. Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain. J. Cell Biol. 131, 1327\u20131340 (1995).","journal-title":"J. Cell Biol."},{"key":"BFnm0896871_CR23","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/0197-4580(95)00057-L","volume":"16","author":"RP Mason","year":"1995","unstructured":"Mason, R.P., Trumbore, M.W. & Pettegrew, J.W. Membrane interactions of a phosphomonoester elevated early in Alzheimer's disease. Neurobiol. Aging 16, 531\u2013539 (1995).","journal-title":"Neurobiol. Aging"},{"issue":"3","key":"BFnm0896871_CR24","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1097\/00002093-198802030-00028","volume":"2","author":"G. S. ZUBENKO","year":"1988","unstructured":"Zubenko, G.S. et al. Platelet membrane fluidity in Alzheimer's disease. Alzheimer Dis. Assoc. Disord. 2, 179 (1988).","journal-title":"Alzheimer Disease & Associated Disorders"},{"key":"BFnm0896871_CR25","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/375754a0","volume":"375","author":"R Sherrington","year":"1995","unstructured":"Sherrington, R. et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754\u2013760 (1995).","journal-title":"Nature"},{"key":"BFnm0896871_CR26","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/376775a0","volume":"376","author":"EI Rogaev","year":"1995","unstructured":"Rogaev, E.I. et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome I related to the Alzheimer's disease type 3 gene. Nature 376, 775\u2013778 (1995).","journal-title":"Nature"},{"key":"BFnm0896871_CR27","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/325733a0","volume":"325","author":"J Kang","year":"1987","unstructured":"Kang, J. et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell surface receptor. Nature 325, 733\u2013736 (1987).","journal-title":"Nature"},{"key":"BFnm0896871_CR28","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/349704a0","volume":"349","author":"A Goate","year":"1991","unstructured":"Goate, A. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704\u2013706 (1991).","journal-title":"Nature"},{"key":"BFnm0896871_CR29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/BF00691849","volume":"62","author":"K Iqbal","year":"1984","unstructured":"Iqbal, K., Zaidi, T., Thompson, C.H., Merz, P.A. & Wisniewski, H.M. Alzheimer paired helical filaments: Bulk isolation, solubility and protein composition. Acta. Neuropathol. (Berl.) 62, 167\u2013177 (1984).","journal-title":"Acta. Neuropathol. (Berl.)"},{"key":"BFnm0896871_CR30","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0003-2697(76)80064-4","volume":"70","author":"A Bensadoun","year":"1976","unstructured":"Bensadoun, A. & Weinstein, D. Assay of proteins in the presence of interfering materials. Anal. Biochem. 70, 241\u2013250 (1976).","journal-title":"Anal. Biochem."},{"key":"BFnm0896871_CR31","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1097\/00005072-198411000-00008","volume":"43","author":"HM Wisniewski","year":"1984","unstructured":"Wisniewski, H.M., Merz, P.A. & Iqbal, K. Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle. J. Neuropathol. Exp. Neurol. 43, 643\u2013656 (1984).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"BFnm0896871_CR32","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/0076-6879(88)59039-0","volume":"159","author":"P Cohen","year":"1988","unstructured":"Cohen, P. et al. Protein phosphatase-1 and protein phosphatase-2A from rabbit skeletal muscle. Methods Enzymol. 159, 390\u2013408 (1988).","journal-title":"Methods Enzymol."},{"key":"BFnm0896871_CR33","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1111\/j.1471-4159.1992.tb09432.x","volume":"59","author":"S Khatoon","year":"1992","unstructured":"Khatoon, S., Grundke-Iqbal, I. & Iqbal, K. Brain levels of microtubule-associated protein tau are elevated in Alzheimer's disease: A radioimmuno-slot-blot assay for nanograms of the protein. J. Neurochem. 59, 750\u2013753 (1992).","journal-title":"J. Neurochem."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm0896-871","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0896-871.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm0896-871.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T23:30:45Z","timestamp":1684452645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm0896-871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,8]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1996,8]]}},"alternative-id":["BFnm0896871"],"URL":"https:\/\/doi.org\/10.1038\/nm0896-871","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,8]]}}}