@article{4a6e79793f0545b381d333fd7c6f5682,
title = "Association between transactive response DNA-binding protein of 43 kDa type and cognitive resilience to Alzheimer's disease: a case-control study",
abstract = "Association between the transactive response DNA-binding protein of 43 kDa (TDP-43), its newly described types (type α/type β), and resilience to Alzheimer's disease neuropathological change (ADNC) defined as preservation of normal cognitive functioning despite advanced ADNC has been evaluated in this case-control study of 63 older adults. Twenty-one resilient to ADNC individuals were matched 1:2 to nonresilient (Alzheimer's dementia) using propensity scores, accounting for age at death, neuritic plaque density, and neurofibrillary tangle stage. Resilient and matched nonresilient participants were similar in terms of gender, apolipoprotein E ε4 carriership, education, occupation, AD, and other pathologies. Resilient participants had lower frequency of TDP-43 co-pathology compared to nonresilient (19% vs. 62%, p = 0.002). Among TDP-43-positive cases, TDP-43 type α inclusions were absent in resilient to ADNC participants and were dominant in matched nonresilient cases (65%, p = 0.03). TDP-43 and TDP-43 types appear to be one of the key pathological determinants of loss of cognitive resilience to ADNC and hence are important in the understanding of the clinical expression of ADNC.",
keywords = "Alzheimer's disease, Cognition, Normal aging, Resilience, TDP-43, TDP-43 types",
author = "Marina Buciuc and Whitwell, {Jennifer L.} and Nirubol Tosakulwong and Weigand, {Stephen D.} and Murray, {Melissa E.} and Boeve, {Bradley F.} and Knopman, {David S.} and Parisi, {Joseph E.} and Petersen, {Ronald C.} and Dickson, {Dennis W.} and Josephs, {Keith A.}",
note = "Funding Information: This study was funded by National Institutes of Health grants R01 AG37491-10 , P50 AG16574 , and U01 AG006786 . These grants served for the design and conduct of the study, collection, management, and analysis of the collected data. TMEM106 genotype was performed by Mr Matthew Baker and Dr Rosa Rademakers, Mayo Clinic, FL. The sponsor had no role in study design; collection, analysis, and interpretation of data; writing the report; or in the decision to submit the article for publication. Funding Information: This study was funded by National Institutes of Health grants R01 AG37491-10, P50 AG16574, and U01 AG006786. These grants served for the design and conduct of the study, collection, management, and analysis of the collected data. TMEM106 genotype was performed by Mr Matthew Baker and Dr Rosa Rademakers, Mayo Clinic, FL. The sponsor had no role in study design; collection, analysis, and interpretation of data; writing the report; or in the decision to submit the article for publication. Buciuc helped in conceptualization, methodology, investigation, formal analysis, and writing original draft; Whitwell helped in conceptualization, methodology, and writing review & editing; Tosakulwong helped in methodology and formal analysis; Weigand helped in methodology, formal analysis, and writing review & editing; Murray helped in investigation, resources, and writing review & editing; Boeve helped in investigation, resources, funding acquisition, and writing review & editing; Knopman helped in investigation, resources, and writing review & editing; Parisi helped in investigation, resources, and writing review & editing; Petersen helped in investigation, resources, funding acquisition, and writing review & editing; Dickson helped in investigation, resources, and writing review & editing; and Josephs helped in conceptualization, methodology, resources, investigation, formal analysis, funding acquisition, supervision, project administration, an writing review & editing. Funding Information: Buciuc, Tosakulwong, Weigand, Murray, Parisi, Dickson, Whitwell, and Josephs do not have conflicts of interest or financial affiliations to disclose. Boeve has served as an investigator for clinical trials sponsored by Biogen and Alector. He serves on the Scientific Advisory Board of the Tau Consortium. He receives research support from the National Institutes of Health, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Lewy Body Dementia Functional Genomics Program. Knopman serves on a Data Safety Monitoring Board for the DIAN study, and is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. Petersen has served on the National Advisory Council on Aging and on the Scientific Advisory Boards of Pfizer, GE Healthcare, Elan Pharmaceuticals, and Janssen Alzheimer Immunotherapy, has received publishing royalties from Oxford University Press, and has been a consultant for Roche Incorporated, Merck, Genentech, Biogen, and Eli Lily. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = aug,
doi = "10.1016/j.neurobiolaging.2020.04.001",
language = "English (US)",
volume = "92",
pages = "92--97",
journal = "Neurobiology of aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
}