Neuropathologic features of TOMM40 ' 523 variant on late-life cognitive decline

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art_YU_Neuropathologic_features_of_TOMM40_523_variant_on_latelife_2017.PDF (740.27 KB)
Citações na Scopus
15
Tipo de produção
article
Data de publicação
2017
Editora
ELSEVIER SCIENCE INC
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
YU, Lei
LUTZ, Michael W.
WILSON, Robert S.
BURNS, Daniel K.
SAUNDERS, Ann M.
JAGER, Philip L. De
BARNES, Lisa L.
SCHNEIDER, Julie A.
BENNETT, David A.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
ALZHEIMERS & DEMENTIA, v.13, n.12, p.1380-1388, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Introduction: The study investigated the role of neuropathologies in the relationship between TOMM40' 523 genotype and late-life cognitive decline. Methods: Participants were community-dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue. Linear mixed models assessed the extent to which the association of '523 genotype with cognitive decline is attributable to neuropathologies. Results: Relative to epsilon 3/epsilon 3 homozygotes with '523-S/VL or '523-VL/VL genotype, both '523-L carriers and epsilon 3/epsilon 3 homozygotes with '523-S/S genotype had faster cognitive decline. The association of '523-L with cognitive decline was attenuated and no longer significant after controlling for Alzheimer's and other neuropathologies. By contrast, the association of '523-S/S was unchanged. Discussion: There are two distinct TOMM40' 523 signals in relation to late-life cognitive decline. One signal primarily acts through AD and other common neuropathologies, whereas the other operates through a different mechanism.
Palavras-chave
Neuropathologies, APOE, TOMM40 ' 523, Alzheimer's disease, Late-life cognitive decline
URI
https://observatorio.fm.usp.br/handle/OPI/25477
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/22