Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample

Autor(es)

Nascimento, Camila ^[1] ; Suemoto, Claudia K. ^{[2, 3]} ; Rodriguez, Roberta D. ^[1] ; Di Lorenzo Alho, Ana Tereza ^{[4, 5]} ; Leite, Renata P. ^{[2, 3]} ; Farfel, Jose Marcelo ^{[2, 3]} ; Goncalves Pasqualucci, Carlos Augusto ^{[6, 3]} ; Jacob-Filho, Wilson ^{[2, 3]} ; Grinberg, Lea T. ^{[6, 3, 7]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Discipline Expt Pathophysiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Div Geriatr, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Brazilian Aging Brain Study Grp, LIM 22, Sao Paulo - Brazil

^[4] Hosp Israelita Albert Einstein, Inst Cerebro, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med, Dept Radiol, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[7] Univ Calif San Francisco, Dept Neurol & Pathol, Memory & Aging Ctr, San Francisco, NC - USA

• Tipo de documento: Artigo Científico
• Fonte: Brain Pathology; v. 26, n. 2, p. 177-185, MAR 2016.
• Citações Web of Science: 13

Resumo

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. (AU)

• Processo FAPESP: 11/19833-7 - Caracterização das alterações da proteína TDP-43 durante o envelhecimento normal: uma análise em cérebros humanos postmortem
• Beneficiário: Camila Nascimento Mantelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/06521-4 - Análise proteômica dos grânulos de neuromelanina no envelhecimento normal e na doença de Parkinson
• Beneficiário: Renata Elaine Paraizo Leite
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/07526-5 - Doença por grãos argirofílicos
• Beneficiário: Roberta Diehl Rodriguez
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto