Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/58031
Title: Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample
Authors: PARADELA, Regina SilvaJUSTO, Alberto Fernando OliveiraPAES, Vitor RibeiroLEITE, Renata E. P.PASQUALUCCI, Carlos A.GRINBERG, Lea T.NASLAVSKY, Michel SatyaZATZ, MayanaNITRINI, RicardoJACOB-FILHO, WilsonSUEMOTO, Claudia Kimie
Citation: ACTA NEUROPATHOLOGICA COMMUNICATIONS, v.11, n.1, article ID 205, 10p, 2023
Abstract: Background: Apolipoprotein E epsilon 4 allele (APOE-epsilon 4) 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-epsilon 4 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-epsilon 4 carriers (at least one epsilon 4 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-epsilon 4 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-epsilon 4 carriers). The association between APOE-epsilon 4 and cognitive abilities was mediated by neurofibrillary tangles (beta = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (beta = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-epsilon 4 to cognition.Conclusion: The association between APOE-epsilon 4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-epsilon 4 and cognition.
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Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MNE
Departamento de Neurologia - FM/MNE

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LIM/15 - Laboratório de Investigação em Neurologia

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LIM/22 - Laboratório de Patolologia Cardiovascular

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LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica

Artigos e Materiais de Revistas Científicas - LIM/66
LIM/66 - Laboratório de Investigação Médica em Envelhecimento


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