APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aß42.
J Neurosci
; 30(50): 17035-40, 2010 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-21159973
ABSTRACT
Identifying high-risk populations is an important component of disease prevention strategies. One approach for identifying at-risk populations for Alzheimer's disease (AD) is examining neuroimaging parameters that differ between patients, including functional connections known to be disrupted within the default-mode network. We have previously shown these same disruptions in cognitively normal elderly who have amyloid-ß (Aß) plaques [detected using Pittsburgh Compound B (PIB) PET imaging], suggesting neuronal toxicity of plaques. Here we sought to determine if pathological effects of apolipoprotein E ε4 (APOE4) genotype could be seen independent of Aß plaque toxicity by examining resting state fMRI functional connectivity (fcMRI) in participants without preclinical fibrillar amyloid deposition (PIB-). Cognitively normal participants enrolled in longitudinal studies (n = 100, mean age = 62) who were PIB- were categorized into those with and without an APOE4 allele and studied using fcMRI. APOE4 allele carriers (E4+) differed significantly from E4- in functional connectivity of the precuneus to several regions previously defined as having abnormal connectivity in a group of AD participants. These effects were observed before any manifestations of cognitive changes and in the absence of brain fibrillar Aß plaque deposition, suggesting that early manifestations of a genetic effect can be detected using fcMRI and that these changes may antedate the pathological effects of fibrillar amyloid plaque toxicity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Placa Amiloide
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Apolipoproteína E4
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Vías Nerviosas
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurosci
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos