Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17

Ming Hong; Victoria Zhukareva; Vanessa Vogelsberg-Ragaglia; Zbigniew Wszolek; Lee Reed; Bruce I. Miller; Dan H. Geschwind; Thomas D. Bird; Daniel McKeel; Alison Coate; John C. Morris; Kirk C. Wilhelmsen; Gerard D. Schellenberg; John Q. Trojanowski; Virginia M.Y. Lee

doi:10.1126/science.282.5395.1914

Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17

Ming Hong, Victoria Zhukareva, Vanessa Vogelsberg-Ragaglia, Zbigniew Wszolek, Lee Reed, Bruce I. Miller, Dan H. Geschwind, Thomas D. Bird, Daniel McKeel, Alison Coate, John C. Morris, Kirk C. Wilhelmsen, Gerard D. Schellenberg, John Q. Trojanowski, Virginia M.Y. Lee

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874 Scopus citations

Abstract

Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.

Original language	English
Pages (from-to)	1914-1917
Number of pages	4
Journal	Science
Volume	282
Issue number	5395
DOIs	https://doi.org/10.1126/science.282.5395.1914
State	Published - 4 Dec 1998
Externally published	Yes

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Hong, M., Zhukareva, V., Vogelsberg-Ragaglia, V., Wszolek, Z., Reed, L., Miller, B. I., Geschwind, D. H., Bird, T. D., McKeel, D., Coate, A., Morris, J. C., Wilhelmsen, K. C., Schellenberg, G. D., Trojanowski, J. Q., & Lee, V. M. Y. (1998). Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science, 282(5395), 1914-1917. https://doi.org/10.1126/science.282.5395.1914

@article{bfba989957c2438dbbdbfe99b096bbbb,

title = "Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17",

abstract = "Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.",

author = "Ming Hong and Victoria Zhukareva and Vanessa Vogelsberg-Ragaglia and Zbigniew Wszolek and Lee Reed and Miller, {Bruce I.} and Geschwind, {Dan H.} and Bird, {Thomas D.} and Daniel McKeel and Alison Coate and Morris, {John C.} and Wilhelmsen, {Kirk C.} and Schellenberg, {Gerard D.} and Trojanowski, {John Q.} and Lee, {Virginia M.Y.}",

year = "1998",

month = dec,

day = "4",

doi = "10.1126/science.282.5395.1914",

language = "English",

volume = "282",

pages = "1914--1917",

journal = "Science",

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number = "5395",

}

Hong, M, Zhukareva, V, Vogelsberg-Ragaglia, V, Wszolek, Z, Reed, L, Miller, BI, Geschwind, DH, Bird, TD, McKeel, D, Coate, A, Morris, JC, Wilhelmsen, KC, Schellenberg, GD, Trojanowski, JQ & Lee, VMY 1998, 'Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17', Science, vol. 282, no. 5395, pp. 1914-1917. https://doi.org/10.1126/science.282.5395.1914

TY - JOUR

T1 - Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17

AU - Hong, Ming

AU - Zhukareva, Victoria

AU - Vogelsberg-Ragaglia, Vanessa

AU - Wszolek, Zbigniew

AU - Reed, Lee

AU - Miller, Bruce I.

AU - Geschwind, Dan H.

AU - Bird, Thomas D.

AU - McKeel, Daniel

AU - Coate, Alison

AU - Morris, John C.

AU - Wilhelmsen, Kirk C.

AU - Schellenberg, Gerard D.

AU - Trojanowski, John Q.

AU - Lee, Virginia M.Y.

PY - 1998/12/4

Y1 - 1998/12/4

N2 - Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.

AB - Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.

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DO - 10.1126/science.282.5395.1914

M3 - Article

C2 - 9836646

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SN - 0036-8075

VL - 282

SP - 1914

EP - 1917

JO - Science

JF - Science

IS - 5395

ER -

Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17

Abstract

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