Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer’s disease pathology: a population-based autopsy study in an admixed sample

Autor: Regina Silva Paradela, Alberto Fernando Oliveira Justo, Vítor Ribeiro Paes, Renata E. P. Leite, Carlos A. Pasqualucci, Lea T. Grinberg, Michel Satya Naslavsky, Mayana Zatz, Ricardo Nitrini, Wilson Jacob-Filho, Claudia Kimie Suemoto
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 11, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 2051-5960
DOI: 10.1186/s40478-023-01681-z
Popis: Abstract Background Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer’s disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. Methods Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). Results We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (β = 0.88, 95% CI = 0.45; 1.38, p
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