Year: 2022
Type: article
Abstract: An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.
Source: Acta Neuropathologica
Authors: Peter T. Nelson, Edward B. Lee, Matthew D. Cykowski, Irina Alafuzoff, Konstantinos Arfanakis, Johannes Attems, Carol Brayne, Maria M. Corrada, Brittany N. Dugger, Margaret E. Flanagan, Bernardino Ghetti, Lea T. Grinberg, Murray Grossman, Michel J. Grothe, Glenda M. Halliday, Masato Hasegawa, Suvi R. K. Hokkanen, Sally Hunter, Kurt Jellinger, Claudia H. Kawas, C. Dirk Keene, Naomi Kouri, Gabor G. Kovacs, James B. Leverenz, Caitlin S. Latimer, Ian R. Mackenzie, Qinwen Mao, Kirsty E. McAleese, Richard Merrick, Thomas J. Montine, Melissa E. Murray, Liisa Myllykangas, Sukriti Nag, Janna H. Neltner, Kathy L. Newell, Robert A. Rissman, Yuko Saito, S. Ahmad Sajjadi, Katherine E. Schwetye, Andrew F. Teich, Dietmar R. Thal, Sandra O. Tomé, Juan C. Troncoso, Shih-Hsiu J. Wang, Charles L. White, Thomas Wisniewski, Hyun-Sik Yang, Julie A. Schneider, Dennis W. Dickson, Manuela Neumann
Institutions: University of Kentucky, University of Pennsylvania, Houston Methodist, Uppsala University, Rush University Medical Center, Illinois Institute of Technology, Newcastle University, University of Cambridge, University of California, Irvine, University of California, Davis, Northwestern University, Northwestern Medicine, Indiana University Indianapolis, University of California, San Francisco, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, The University of Sydney, Tokyo Metropolitan Institute of Medical Science, University of Washington, Mayo Clinic in Florida, University Health Network, University of Toronto, Medical University of Vienna, Cleveland Clinic, University of British Columbia, University of Utah, Stanford University, University of Helsinki, Helsinki University Hospital, University of California San Diego, Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital, Washington University in St. Louis, Columbia University, Universitair Ziekenhuis Leuven, KU Leuven, Johns Hopkins University, Duke University, The University of Texas Southwestern Medical Center, New York University, Brigham and Women's Hospital, Harvard University, University of Tübingen
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funders: California Department of Public Health, BrightFocus Foundation, Nancy and Buster Alvord Endowment, Japan Agency for Medical Research and Development, Alzheimer Forschung Initiative, Alzheimer's Society, National Institute for Health and Care Research, Fonds Wetenschappelijk Onderzoek, NOMIS Stiftung, Vlaamse regering, Rossy Foundation, National Institutes of Health, University of California, Davis, Alzheimer’s Disease Research Center, University of Washington, Medical Research Council, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, European Regional Development Fund, NIHR Cambridge Biomedical Research Centre, National Institute on Aging
Awards: G1045600774, Risk factors for neuropathological hallmark lesions and cell death in preclinical and symptomatic Alzheimer’s disease: a chance for age-of-onset prediction?, Indiana Alzheimer Disease Center, G1487101512, G1782808350, Novel Approaches to Understand the Pathogenesis and Treat Alzheimer's Disease, G1993074849, Investigating TDP-43 biology in Alzheimer’s Disease and LATE: impact on the clinical diagnosis, G2147220212, Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias, Molecular Mechanisms of Synergistic TDP-43 and Tau Proteotoxicity in Alzheimer's Disease, G2637832891, Age-related TDP-43 neuropathology: using disease-driving mechanisms to guide classification, G366407493, G3721581127, "What is N?" Towards operationalizing neurodegeneration in Alzheimer's and related dementias, G4013433402, Clinicopathologic and Neuroimaging Differences in Alzheimer's Disease Variants, G4540457744, G4604477821, Neuropathologic substrates for motor and cognitive impairment in three existing cohort studies of Alzheimer's disease and related dementias, The role of protein aggregate maturation in Alzheimer's disease and other neurodegenerative disorders and its potential for disease monitoring and differential diagnosis., G581645544, G5870618905, G5938933245, Utah Center for Clinical and Translational Science, G6310099081, Immunogenetic contribution to the progression of preclinical Alzheimer's disease, G6720564865, Platform of Supporting Cohort Study and Biospecimen Analysis, G6990300350, Characterizing TDP-43 related hippocampal degeneration and memory loss in aging, G7686550736, Estudio de la heterogeneidad fisiopatológica subyacente al deterioro cognitivo y la demencia en la enfermedad de Parkinson, nvestigating the role of neuroinflammation in Limbic-predominant age related TDP43 encephalopathy, G8376115369, In-vivo MRI-based prediction of TDP43 pathology in aging, G8874875879, G888387902, G9000014109, G9000037693, G9000055340, G9000085578, G9000087139, G9000091371, G9000112075, G9000115163, G9000116369, G9000122335, G9000134521, G9000148901, G9000172197, G9000179856, G9000182597, G9000183948, G9000205596, G9000243838, G9000246517, G9000259012, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Adult Changes in Thought (ACT) Research Program, UC Davis Alzheimer's Disease Research Center, Neuropathological changes underlying clinical heterogeneity in Alzheimer dise, Diagnosis and Risk factors of hippocampal sclerosis of aging and limbic predominant age related TDP-43 encephalopathy; common Alzheimer’s mimics, Johns Hopkins Alzheimer's Disease Research Center, Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSP, Indiana Alzheimer's Disease Research Center, University of Washington Alzheimer's Disease Research Center, Alzheimer's Disease Research Centers, University of Kentucky Alzheimer's Disease Research Center, Penn Alzheimer's Disease Research Center (ADRC), National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
OpenAlex ID: W4311237378