Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain

Jeanna M. Wheeler; Pamela McMillan; Timothy J. Strovas; Nicole F. Liachko; Alexandre Amlie-Wolf; Rebecca L. Kow; Ronald L. Klein; Patricia Szot; Linda Robinson; Chris Guthrie; Aleen Saxton; Nicholas M. Kanaan; Murray Raskind; Elaine Peskind; John Q. Trojanowski; Virginia M. Y. Lee; Li-San Wang; C. Dirk Keene; Thomas Bird; Gerard D. Schellenberg; Brian Kraemer

doi:10.1126/scitranslmed.aao6545

Research ArticleAlzheimer’s Disease

Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain

Jeanna M. Wheeler¹,*,
Pamela McMillan²,*,
Timothy J. Strovas¹,*,
Nicole F. Liachko ¹,³,
Alexandre Amlie-Wolf⁴,
Rebecca L. Kow¹,³,
Ronald L. Klein⁵,†,
Patricia Szot²,⁶,
Linda Robinson¹,
Chris Guthrie¹,
Aleen Saxton¹,
Nicholas M. Kanaan⁷,
Murray Raskind²,⁶,
Elaine Peskind²,⁶,
John Q. Trojanowski⁴,
Virginia M. Y. Lee ⁴,
Li-San Wang⁴,
C. Dirk Keene ⁸,
Thomas Bird¹,⁹,¹⁰,
Gerard D. Schellenberg ⁴ and
Brian Kraemer ¹,²,³,⁸,‡

¹Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
²Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
³Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
⁴Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁵Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
⁶Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
⁷Department of Translational Sciences and Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
⁸Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
⁹Department of Neurology, University of Washington School of Medicine, Seattle, WA 98195, USA.
¹⁰Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98104, USA.

↵‡Corresponding author. Email: kraemerb{at}uw.edu

↵* These authors contributed equally to this work.
↵† Deceased.

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Science Translational Medicine 18 Dec 2019:
Vol. 11, Issue 523, eaao6545
DOI: 10.1126/scitranslmed.aao6545

Jeanna M. Wheeler

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Pamela McMillan

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

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Timothy J. Strovas

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Nicole F. Liachko

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.

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Alexandre Amlie-Wolf

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Rebecca L. Kow

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.

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Ronald L. Klein

Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.

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Patricia Szot

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Linda Robinson

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Chris Guthrie

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Aleen Saxton

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Nicholas M. Kanaan

Department of Translational Sciences and Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.

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Murray Raskind

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Elaine Peskind

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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John Q. Trojanowski

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Virginia M. Y. Lee

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Li-San Wang

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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C. Dirk Keene

Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.

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Thomas Bird

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

Department of Neurology, University of Washington School of Medicine, Seattle, WA 98195, USA.

Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98104, USA.

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Gerard D. Schellenberg

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Brian Kraemer

Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.

Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.

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For correspondence: kraemerb@uw.edu

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Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain

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