DOI: 10.1073/pnas.94.1.298. Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau

Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau

10.1073/pnas.94.1.298

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The microtubule-associated protein (MAP) tau is abnormally hyperphosphorylated in Alzheimer disease and accumulates in neurons undergoing neurofibrillary degeneration. In the present study, the associations of the Alzheimer-hyperphosphorylated tau (AD P-tau) with the high molecular weight MAPs (HMW-MAPs) MAP1 and MAP2 were investigated. The AD P-tau was found to aggregate with MAP1 and MAP2 in solution. The association of AD P-tau to the MAPs resulted in inhibition of MAP-promoted microtubule assembly. However, unlike the coaggregation of AD P-tau and normal tau, the association between AD P-tau and the HMW-MAPs did not result in the formation of filaments/tangles. The affinity of the tau–AD P-tau association was higher than that of HMW-MAPs–AD P-tau because normal tau inhibited the latter binding. The association between AD P-tau and the HMW-MAPs also appeared to occur in situ because these proteins cosedimented from the Alzheimer brain extracts, and, in the sediment, the levels of the HMW-MAPs correlated with the levels of AD P-tau. These studies suggested that the abnormally phosphorylated tau can sequester both normal tau and HMW-MAPs and disassemble microtubules but, under physiological conditions, can form tangles of filaments only from tau.

Bibliography

Alonso, A. del C., Grundke-Iqbal, I., Barra, H. S., & Iqbal, K. (1997). Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormalâtau. Proceedings of the National Academy of Sciences, 94(1), 298â303.

Authors 4

Alejandra del C. Alonso (first)
Inge Grundke-Iqbal (additional)
Héctor S. Barra (additional)
Khalid Iqbal (additional)

References 27 Referenced 330

Iqbal K. Grundke-Iqbal I. Zaidi T. Merz P. A. Wen G. Y. Shaikh S. S. Wisniewski H. M. Alafuzoff I. & Wimblad B. (1986) Lancet ii 421–426. (10.1016/S0140-6736(86)92134-3)
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10.1038/nm0896-871
10.1016/0169-328X(95)00316-K
10.1038/nm0796-783
10.1016/0306-4522(90)90201-E
J Avila, J Domínguez, J Díaz-Nido Int J Dev Biol 38, 13–25 (1994). / Int J Dev Biol by Avila J (1994)
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10.1111/j.1471-4159.1993.tb03603.x
10.1046/j.1471-4159.1995.65020732.x

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:43 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:48 p.m.)
Indexed	6 days, 15 hours ago (Aug. 24, 2025, 6:58 p.m.)
Issued	28 years, 7 months ago (Jan. 7, 1997)
Published	28 years, 7 months ago (Jan. 7, 1997)
Published Online	28 years, 7 months ago (Jan. 7, 1997)
Published Print	28 years, 7 months ago (Jan. 7, 1997)

Funders 0

None

BibTeX

@article{Alonso_1997, title={Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.1.298}, DOI={10.1073/pnas.94.1.298}, number={1}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Alonso, Alejandra del C. and Grundke-Iqbal, Inge and Barra, Héctor S. and Iqbal, Khalid}, year={1997}, month=jan, pages={298–303} }

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