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

View ORCID ProfileJeanna M. Wheeler¹,*,
View ORCID ProfilePamela McMillan²,*,
View ORCID ProfileTimothy J. Strovas¹,*,
View ORCID ProfileNicole F. Liachko ¹,³,
View ORCID ProfileAlexandre Amlie-Wolf⁴,
View ORCID ProfileRebecca L. Kow¹,³,
Ronald L. Klein⁵,†,
View ORCID ProfilePatricia Szot²,⁶,
View ORCID ProfileLinda Robinson¹,
View ORCID ProfileChris Guthrie¹,
View ORCID ProfileAleen Saxton¹,
View ORCID ProfileNicholas M. Kanaan⁷,
View ORCID ProfileMurray Raskind²,⁶,
View ORCID ProfileElaine Peskind²,⁶,
View ORCID ProfileJohn Q. Trojanowski⁴,
Virginia M. Y. Lee ⁴,
View ORCID ProfileLi-San Wang⁴,
View ORCID ProfileC. Dirk Keene ⁸,
Thomas Bird¹,⁹,¹⁰,
View ORCID ProfileGerard D. Schellenberg ⁴ and
View ORCID ProfileBrian 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

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Pamela McMillan

2Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

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Timothy J. Strovas

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Nicole F. Liachko

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

3Division 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

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Rebecca L. Kow

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

3Division 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

5Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.

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Patricia Szot

2Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

6Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Linda Robinson

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Chris Guthrie

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Aleen Saxton

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Nicholas M. Kanaan

7Department of Translational Sciences and Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.

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Murray Raskind

2Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

6Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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Elaine Peskind

2Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

6Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

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John Q. Trojanowski

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Virginia M. Y. Lee

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Li-San Wang

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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C. Dirk Keene

8Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.

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Thomas Bird

1Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, 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.

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Gerard D. Schellenberg

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Brian Kraemer

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.

8Department 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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