C Nascimento1, A T Di Lorenzo Alho2,3, C Bazan Conceição Amaral4, R E P Leite5, R Nitrini6, W Jacob-Filho5, C A Pasqualucci4, S R K Hokkanen7, S Hunter7, H Keage8, G G Kovacs9, L T Grinberg4,10, C K Suemoto5. 1. Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. 2. Department of Radiology, University of São Paulo Medical School, São Paulo, Brazil. 3. Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, Brazil. 4. Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil. 5. Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil. 6. Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil. 7. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 8. Social Work and Social Policy, School of Psychology, University of South Australia, Adelaide, SA, Australia. 9. Institute of Neurology, Medical University of Vienna, Vienna, Austria. 10. Department of Neurology, Memory and Aging Center, University of San Francisco, San Francisco, CA, USA.
Abstract
OBJECTIVE: To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS: We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. RESULTS: A total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. CONCLUSIONS: Different methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
OBJECTIVE: To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS: We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. RESULTS: A total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. CONCLUSIONS: Different methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
Authors: Sukriti Nag; Lei Yu; Ana W Capuano; Robert S Wilson; Sue E Leurgans; David A Bennett; Julie A Schneider Journal: Ann Neurol Date: 2015-04-22 Impact factor: 10.422
Authors: Jose Marcelo Farfel; Ricardo Nitrini; Claudia Kimie Suemoto; Lea Tenenholz Grinberg; Renata Eloah Lucena Ferretti; Renata Elaine Paraizo Leite; Edilaine Tampellini; Luzia Lima; Daniela Souza Farias; Ricardo Caires Neves; Roberta Diehl Rodriguez; Paulo Rossi Menezes; Felipe Fregni; David A Bennett; Carlos Augusto Pasqualucci; Wilson Jacob Filho Journal: Neurology Date: 2013-07-19 Impact factor: 9.910
Authors: Felix Geser; Maria Martinez-Lage; John Robinson; Kunihiro Uryu; Manuela Neumann; Nicholas J Brandmeir; Sharon X Xie; Linda K Kwong; Lauren Elman; Leo McCluskey; Chris M Clark; Joe Malunda; Bruce L Miller; Earl A Zimmerman; Jiang Qian; Vivianna Van Deerlin; Murray Grossman; Virginia M-Y Lee; John Q Trojanowski Journal: Arch Neurol Date: 2009-02
Authors: Irina Alafuzoff; Thomas Arzberger; Safa Al-Sarraj; Istvan Bodi; Nenad Bogdanovic; Heiko Braak; Orso Bugiani; Kelly Del-Tredici; Isidro Ferrer; Ellen Gelpi; Giorgio Giaccone; Manuel B Graeber; Paul Ince; Wouter Kamphorst; Andrew King; Penelope Korkolopoulou; Gábor G Kovács; Sergey Larionov; David Meyronet; Camelia Monoranu; Piero Parchi; Efstratios Patsouris; Wolfgang Roggendorf; Danielle Seilhean; Fabrizio Tagliavini; Christine Stadelmann; Nathalie Streichenberger; Dietmar R Thal; Stephen B Wharton; Hans Kretzschmar Journal: Brain Pathol Date: 2008-03-26 Impact factor: 6.508
Authors: Alexandra M Wennberg; Jennifer L Whitwell; Nirubol Tosakulwong; Stephen D Weigand; Melissa E Murray; Mary M Machulda; Leonard Petrucelli; Michelle M Mielke; Clifford R Jack; David S Knopman; Joseph E Parisi; Ronald C Petersen; Dennis W Dickson; Keith A Josephs Journal: Neurobiol Aging Date: 2019-01-21 Impact factor: 4.673
Authors: Alexandre Bejanin; Melissa E Murray; Peter Martin; Hugo Botha; Nirubol Tosakulwong; Christopher G Schwarz; Matthew L Senjem; Gael Chételat; Kejal Kantarci; Clifford R Jack; Bradley F Boeve; David S Knopman; Ronald C Petersen; Caterina Giannini; Joseph E Parisi; Dennis W Dickson; Jennifer L Whitwell; Keith A Josephs Journal: Brain Date: 2019-11-01 Impact factor: 13.501
Authors: Adam M Staffaroni; Jesse A Brown; Kaitlin B Casaletto; Fanny M Elahi; Jersey Deng; John Neuhaus; Yann Cobigo; Paige S Mumford; Samantha Walters; Rowan Saloner; Anna Karydas; Giovanni Coppola; Howie J Rosen; Bruce L Miller; William W Seeley; Joel H Kramer Journal: J Neurosci Date: 2018-02-13 Impact factor: 6.167
Authors: Eun-Joo Kim; Jesse A Brown; Jersey Deng; Ji-Hye L Hwang; Salvatore Spina; Zachary A Miller; Mary G DeMay; Victor Valcour; Anna Karydas; Eliana Marisa Ramos; Giovanni Coppola; Bruce L Miller; Howard J Rosen; William W Seeley; Lea T Grinberg Journal: J Neurol Date: 2018-10-15 Impact factor: 4.849
Authors: Peter T Nelson; Carol Brayne; Margaret E Flanagan; Erin L Abner; Sonal Agrawal; Johannes Attems; Rudolph J Castellani; Maria M Corrada; Matthew D Cykowski; Jing Di; Dennis W Dickson; Brittany N Dugger; John F Ervin; Jane Fleming; Jonathan Graff-Radford; Lea T Grinberg; Suvi R K Hokkanen; Sally Hunter; Alifiya Kapasi; Claudia H Kawas; Hannah A D Keage; C Dirk Keene; Mia Kero; David S Knopman; Naomi Kouri; Gabor G Kovacs; Sydney A Labuzan; Eric B Larson; Caitlin S Latimer; Renata E P Leite; Billie J Matchett; Fiona E Matthews; Richard Merrick; Thomas J Montine; Melissa E Murray; Liisa Myllykangas; Sukriti Nag; Ruth S Nelson; Janna H Neltner; Aivi T Nguyen; Ronald C Petersen; Tuomo Polvikoski; R Ross Reichard; Roberta D Rodriguez; Claudia K Suemoto; Shih-Hsiu J Wang; Stephen B Wharton; Lon White; Julie A Schneider Journal: Acta Neuropathol Date: 2022-06-13 Impact factor: 15.887
Authors: Margaret E Flanagan; Brenna Cholerton; Caitlin S Latimer; Laura S Hemmy; Steven D Edland; Kathleen S Montine; Lon R White; Thomas J Montine Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Peter T Nelson; Dennis W Dickson; John Q Trojanowski; Clifford R Jack; Patricia A Boyle; Konstantinos Arfanakis; Rosa Rademakers; Irina Alafuzoff; Johannes Attems; Carol Brayne; Ian T S Coyle-Gilchrist; Helena C Chui; David W Fardo; Margaret E Flanagan; Glenda Halliday; Suvi R K Hokkanen; Sally Hunter; Gregory A Jicha; Yuriko Katsumata; Claudia H Kawas; C Dirk Keene; Gabor G Kovacs; Walter A Kukull; Allan I Levey; Nazanin Makkinejad; Thomas J Montine; Shigeo Murayama; Melissa E Murray; Sukriti Nag; Robert A Rissman; William W Seeley; Reisa A Sperling; Charles L White; Lei Yu; Julie A Schneider Journal: Brain Date: 2019-06-01 Impact factor: 15.255