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Primary age-related tauopathy (PART): a common pathology associated with human aging

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Abstract

We recommend a new term, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer’s disease (AD), in the absence of amyloid (Aβ) plaques. For these “NFT+/Aβ−” brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as “tangle-only dementia” and “tangle-predominant senile dementia”, are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.

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Acknowledgments

We are extremely grateful to the patients, clinicians, and fellow researchers that made this effort possible. We also acknowledge the following funding sources: the Society for Supporting Research in Experimental Neurology, Vienna, Austria, National Institutes of Health Grants P50AG08702, R01 AG037212, P01AG07232, P30 AG028383, P50 AG005138, P50 AG016574, U01 AG006786, R01 AG041851, R01 AG011378, P30 AG028383, P50 AG016574, P01 AG003949, P30 AG012300, P50 AG005146, P50 AG005136, P50 AG025688, P50 AG005138, P01 AG002219, P50 AG005133, P50 AG005681, P01 AG003991, R01 AG038651, P30 AG019610, P30 AG013854, P30 AG036453, P30 AG010124, AG005131, AG184440, AG008051, Medical Research Council (MRC, G0400074), National Institute for Health Research (NIHR, R:CH/ML/0712), the Dunhill Medical Trust (R173/1110), Alzheimer’s Research UK (ARUK), and the Alzheimer’s Society (AS-PG-2013-011), Louis V. Gerstner, Jr., Foundation, Alzheimer’s Association (NIRG-11-204450), FP7 EU Project Develage (No. 278486), Comprehensive brain research network, Grant-in-Aid for Scientific Research (C; 26430060), and Daiwa Health Science Foundation, BrightFocus Foundation, Alzheimer’s Association NIRGD-12-242642, Alzheimer Forschung Initiative (AFI # 13803) (DRT); German Ministry for Research and Education (BMBF) FTLD-Net, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation.

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Authors and Affiliations

  1. Department of Pathology and Cell Biology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, New York, NY, 10032, USA

    John F. Crary, Ismael Santa-Maria, Michael L. Shelanski & Jean Paul Vonsattel

  2. Department of Pathology, Division of Neuropathology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    John Q. Trojanowski & Jonathan B. Toledo

  3. Departments of Pathology (Neuropathology) and Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA

    Julie A. Schneider

  4. Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Jose F. Abisambra

  5. Department of Public Health and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Erin L. Abner

  6. Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85, Uppsala, Sweden

    Irina Alafuzoff

  7. Departments of Psychiatry and Neurology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Steven E. Arnold

  8. Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE45PL, UK

    Johannes Attems

  9. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, 85351, USA

    Thomas G. Beach

  10. Department of Pathology (Neuropathology), Northwestern Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Eileen H. Bigio

  11. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Nigel J. Cairns

  12. Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Dennis W. Dickson & Melissa E. Murray

  13. Department of Pathology and Laboratory Medicine (Neuropathology), Emory University School of Medicine, Atlanta, GA, 30322, USA

    Marla Gearing

  14. Departments of Neurology and Pathology, UC, San Francisco, CA, 94110, USA

    Lea T. Grinberg

  15. Department of Pathology, University of Sao Paulo, Sao Paulo, Brazil

    Lea T. Grinberg

  16. Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Patrick R. Hof

  17. Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Charlestown, MA, 02129, USA

    Bradley T. Hyman

  18. Institute of Clinical Neurobiology, 1070, Vienna, Austria

    Kurt Jellinger

  19. Department of Neurology and the Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA

    Gregory A. Jicha

  20. Institute of Neurology, Medical University Vienna, 1090, Vienna, Austria

    Gabor G. Kovacs

  21. Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA

    David S. Knopman

  22. Department of Pathology (Neuropathology), University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA

    Julia Kofler

  23. Department of Epidemiology, University of Washington, Seattle, WA, 98104, USA

    Walter A. Kukull

  24. Department of Pathology, University of British Columbia, 855 West 12th Avenue, Vancouver, BC, V5Z 1M9, Canada

    Ian R. Mackenzie

  25. Departments of Neurosciences and Pathology, University of California, San Diego, La Jolla, CA, 92093, USA

    Eliezer Masliah

  26. Department of Pathology (Neuropathology), Boston University, Boston, MA, 02118, USA

    Ann McKee

  27. Department of Pathology, University of Washington, Seattle, WA, 98104, USA

    Thomas J. Montine

  28. Department of Pathology, University of Kentucky, Lexington, KY, 40536, USA

    Janna H. Neltner

  29. Departments of Neurology and Pathology, University of California, San Francisco, CA, 94143, USA

    William W. Seeley

  30. Department of Neurology, University of Iowa Hospitals and Clinics, Iowa city, IA, 52242, USA

    Alberto Serrano-Pozo

  31. Department of Pathology (Neuropathology), VA Medical Center and Boston University School of Medicine, Boston, MA, 02118, USA

    Thor Stein

  32. Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, 173-0015, Japan

    Masaki Takao

  33. Laboratory of Neuropathology, University of Ulm, 89081, Ulm, Germany

    Dietmar R. Thal

  34. Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Juan C. Troncoso

  35. Department of Pathology (Neuropathology), University of Texas Southwestern Medical School, Dallas, TX, 75390, USA

    Charles L. White 3rd

  36. Departments of Neurology, Pathology and Psychiatry, New York University School of Medicine, New York, NY, 10016, USA

    Thomas Wisniewski

  37. Department of Pathology L113, Oregon Health Sciences University, Portland, OR, 97239, USA

    Randall L. Woltjer

  38. Departments of Neurology & Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan

    Masahito Yamada

  39. Department of Pathology (Neuropathology) and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Peter T. Nelson

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Correspondence to John F. Crary or Peter T. Nelson.

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Crary, J.F., Trojanowski, J.Q., Schneider, J.A. et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128, 755–766 (2014). https://doi.org/10.1007/s00401-014-1349-0

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