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Research Article

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

  • Richard J. Perrin equal contributor mail,

    equal contributor Contributed equally to this work with: Richard J. Perrin, Rebecca Craig-Schapiro

    rperrin@path.wustl.edu

    Affiliations: Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Rebecca Craig-Schapiro equal contributor,

    equal contributor Contributed equally to this work with: Richard J. Perrin, Rebecca Craig-Schapiro

    Affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • James P. Malone,

    Affiliations: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Division of Metabolism and Proteomics Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Aarti R. Shah,

    Affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Petra Gilmore,

    Affiliations: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Division of Metabolism and Proteomics Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Alan E. Davis,

    Affiliations: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Division of Metabolism and Proteomics Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Catherine M. Roe,

    Affiliations: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Elaine R. Peskind,

    Affiliations: Department of Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, University of Washington School of Medicine, Seattle, Washington, United States of America, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, United States of America

    X
  • Ge Li,

    Affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, United States of America

    X
  • Douglas R. Galasko,

    Affiliation: Department of Neurosciences, University of California at San Diego, San Diego, California, United States of America

    X
  • Christopher M. Clark,

    Affiliations: Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, Alzheimer's Disease Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, United States of America

    X
  • Joseph F. Quinn,

    Affiliation: Layton Aging and Alzheimer's Disease Center, Oregon Health Science University, Portland, Oregon, United States of America

    X
  • Jeffrey A. Kaye,

    Affiliation: Layton Aging and Alzheimer's Disease Center, Oregon Health Science University, Portland, Oregon, United States of America

    X
  • John C. Morris,

    Affiliations: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • David M. Holtzman,

    Affiliations: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Division of Metabolism and Proteomics Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • R. Reid Townsend,

    Affiliations: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Division of Metabolism and Proteomics Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

    X
  • Anne M. Fagan

    Affiliations: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, United States of America

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  • Published: January 12, 2011
  • DOI: 10.1371/journal.pone.0016032

About the Authors

Richard J. Perrin
Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri, United States of America
Richard J. Perrin, John C. Morris
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
Richard J. Perrin, Catherine M. Roe, John C. Morris, David M. Holtzman, Anne M. Fagan
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, United States of America
Rebecca Craig-Schapiro, Aarti R. Shah, Catherine M. Roe, John C. Morris, David M. Holtzman, Anne M. Fagan
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America
James P. Malone, Petra Gilmore, Alan E. Davis, David M. Holtzman, R. Reid Townsend
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
James P. Malone, Petra Gilmore, Alan E. Davis, David M. Holtzman, R. Reid Townsend
Division of Metabolism and Proteomics Center, Washington University School of Medicine, St. Louis, Missouri, United States of America
David M. Holtzman, Anne M. Fagan
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, United States of America
Elaine R. Peskind
Department of Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, University of Washington School of Medicine, Seattle, Washington, United States of America
Elaine R. Peskind, Ge Li
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, United States of America
Douglas R. Galasko
Department of Neurosciences, University of California at San Diego, San Diego, California, United States of America
Christopher M. Clark
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Christopher M. Clark
Alzheimer's Disease Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Christopher M. Clark
Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, United States of America
Joseph F. Quinn, Jeffrey A. Kaye
Layton Aging and Alzheimer's Disease Center, Oregon Health Science University, Portland, Oregon, United States of America

Corresponding Author

Email: rperrin@path.wustl.edu

Competing Interests

D.M.H. co-founded C2N Diagnostics, is on the scientific advisory board of C2N Diagnostics, En Vivo, and Satori, consulted for Pfizer, and receives grants that did not support this work from Eli Lilly, Pfizer, and Astra-Zeneca. J.C.M. has consulted for Astra Zeneca, Genentech, and Merck, has received honoraria from ANA Soriano lecture, payment from Journal Watch for preparation of other manuscripts, royalties from Blackwell Publishers and Taylor and Francis, and travel funding for ANA meeting Baltimore. C.M.C. became emeritus at University of Pennsylvania on January 1, 2010, and now works for Avid Radiopharmaceuticals, which did not provide any funding for this study, and did not have any involvement or influence in data production, data analysis, decision to publish, or manuscript preparation. None of the above stated competing interests alter our adherence to all the PLoS ONE policies on sharing data and materials.

Author Contributions

Conceived and designed the experiments: RJP RC-S DMH JCM AMF RRT. Performed the experiments: RJP RC-S JPM AED PG RRT ARS. Analyzed the data: RJP RC-S JPM AED PG RRT ARS CMR DMH AMF. Contributed reagents/materials/analysis tools: RRT ERP GL DRG CMC JFQ JAK DMH JCM AMF. Wrote the paper: RJP RC-S JPM RRT. All authors revised the manuscript for important intellectual content and gave final approval of the version to be published.