National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (original) (raw)

Abstract

We present a practical guide for the implementation of recently revised National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an “ABC” score for AD neuropathologic change that incorporates histopathologic assessments of amyloid β deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations.

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Acknowledgments

Support was provided by the National Institute on Aging (AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976, AG16570, AG15866 and AG18840) as well as the Alzheimer’s Association, Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Consortium), Deutsche Forschungsgemeinschaft (DFG TH-624-4-1) and Alzheimer Forschung Initiative (AFI #10810), the Nancy and Buster Alvord Endowment, and the Charles and Joanne Knight Alzheimer Research Initiative. We thank Dr. Joshua Sonnen for providing some photomicrographs. The authors extend their deepest thanks to Dr. Heiko Braak, Dr. Kelly Del Tredici, Dr. Nina Silverberg, Dr. Walter Kukull, Dr. Kathleen Montine, Dr. Cerise Elliott, Dr. Bill Thies, Dr. Maria C. Carrillo, and Ms. Sarah Monsell for their valuable input.

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Authors and Affiliations

  1. Department of Pathology, University of Washington School of Medicine, Box 359791, Seattle, WA, 98104, USA
    Thomas J. Montine
  2. National Institute on Aging, Bethesda, MD, USA
    Creighton H. Phelps
  3. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA
    Thomas G. Beach
  4. Department of Pathology and Northwestern Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Eileen H. Bigio
  5. Departments of Neurology and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
    Nigel J. Cairns
  6. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Dennis W. Dickson
  7. Service de Neuropathologie Raymond Escourolle, Hôpital de la Salpêtriére, Paris, France
    Charles Duyckaerts
  8. C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Matthew P. Frosch
  9. Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA
    Eliezer Masliah
  10. Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, USA
    Suzanne S. Mirra
  11. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA
    Peter T. Nelson
  12. Departments of Pathology and Neurological Sciences, Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
    Julie A. Schneider
  13. Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Ulm, Germany
    Dietmar Rudolf Thal
  14. Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    John Q. Trojanowski
  15. Departments of Pathology & Laboratory Medicine (Neuropathology) and Neurology, University of California Los Angeles, Los Angeles, CA, USA
    Harry V. Vinters
  16. Neurology Department, Massachusetts General Hospital, Harvard University, Boston, MA, USA
    Bradley T. Hyman

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  1. Thomas J. Montine
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  2. Creighton H. Phelps
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  3. Thomas G. Beach
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  4. Eileen H. Bigio
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  5. Nigel J. Cairns
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  6. Dennis W. Dickson
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  7. Charles Duyckaerts
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  8. Matthew P. Frosch
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  9. Eliezer Masliah
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  10. Suzanne S. Mirra
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  11. Peter T. Nelson
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  12. Julie A. Schneider
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  13. Dietmar Rudolf Thal
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  14. John Q. Trojanowski
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  15. Harry V. Vinters
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  16. Bradley T. Hyman
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Correspondence toThomas J. Montine.

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Montine, T.J., Phelps, C.H., Beach, T.G. et al. National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach.Acta Neuropathol 123, 1–11 (2012). https://doi.org/10.1007/s00401-011-0910-3

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