title: Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample.
abstract: Transactive response DNA binding protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer's disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP-43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy was identified in 10.5%, independently associated with older age (P = 0.03) and Asian ethnicity (P = 0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage and schooling (odds ratio = 3.50, confidence interval 1.41-8.69, P = 0.007). These findings suggested that Asian older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies.
authors.affiliation: Discipline of Experimental Pathophysiology, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Nascimento
authors.affiliation: Division of Geriatrics, University of Sao Paulo Medical School, São Paulo, Brazil.|Brazilian Aging Brain Study Group, LIM-22, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Claudia K
authors.initials: CK
authors.lastname: Suemoto
authors.affiliation: Discipline of Experimental Pathophysiology, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Roberta D
authors.initials: RD
authors.lastname: Rodriguez
authors.affiliation: Department of Radiology, University of Sao Paulo Medical School, São Paulo, Brazil.|Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Ana Tereza Di Lorenzo
authors.initials: AT
authors.lastname: Alho
authors.affiliation: Division of Geriatrics, University of Sao Paulo Medical School, São Paulo, Brazil.|Brazilian Aging Brain Study Group, LIM-22, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Renata P
authors.initials: RP
authors.lastname: Leite
authors.affiliation: Division of Geriatrics, University of Sao Paulo Medical School, São Paulo, Brazil.|Brazilian Aging Brain Study Group, LIM-22, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Jose Marcelo
authors.initials: JM
authors.lastname: Farfel
authors.affiliation: Brazilian Aging Brain Study Group, LIM-22, University of Sao Paulo Medical School, São Paulo, Brazil.|Department of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Carlos Augusto Gonçalves
authors.initials: CA
authors.lastname: Pasqualucci
authors.affiliation: Division of Geriatrics, University of Sao Paulo Medical School, São Paulo, Brazil.|Brazilian Aging Brain Study Group, LIM-22, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Jacob-Filho
authors.affiliation: Brazilian Aging Brain Study Group, LIM-22, University of Sao Paulo Medical School, São Paulo, Brazil.|Department of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.|Memory and Aging Center, Department of Neurology and Pathology, University of California, San Francisco, NC.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
mesh_terms: D000367:Age Factors; D000368:Aged; D044466:Asian People; D044383:Black People; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003071:Cognition; D004522:Educational Status; D005260:Female; D006801:Humans; D008297:Male; D015995:Prevalence; D012720:Severity of Illness Index; D012737:Sex Factors; D057177:TDP-43 Proteinopathies / Q000208:ethnology* / Q000378:metabolism / Q000473:pathology*; D044465:White People
keywords: Asian; TDP-43 proteinopathy; autopsy; cognitively normal elderly; dementia; postmortem; race