AD and non-AD mediators of the pathway between the APOE genotype and cognition.
Alzheimers Dement
; 19(6): 2508-2519, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-36516004
ABSTRACT
INTRODUCTION:
The apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late-life cognition through Alzheimer's disease (AD) and non-AD neuropathologies.METHODS:
We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aß), neurofibrillary tangles), vascular (athero/arteriolo-sclerosis, micro-infarcts/macro-infarcts), and non-AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP-43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis).RESULTS:
The detrimental effect of APOE ε4 on cognition was mediated by summary measures of AD and non-AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE ε2 was partly mediated by AD neuropathology and stronger in women than in men.DISCUSSION:
The APOE genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia. HIGHLIGHTS Both apolipoprotein E (APOE) ε2 and APOE ε4 effects on late-life cognition are mediated by AD neuropathology. The estimated mediated effects of most measures of AD neuropathology were similar. Non-Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of ε4 independently from AD. Non-AD vascular pathologies did not mediate the effect of the APOE genotype on cognition. The protective effect of APOE ε2 on cognition was stronger in women.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteína E4
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Enfermedad de Alzheimer
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Alzheimers Dement
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos