Prenatal high-fat diet alters the cerebrovasculature and clearance of ß-amyloid in adult offspring.
J Pathol
; 235(4): 619-31, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25345857
ABSTRACT
Alzheimer's disease (AD) is characterized by the accumulation of ß-amyloid (Aß) peptides in the extracellular spaces of the brain as plaques and in the walls of blood vessels as cerebral amyloid angiopathy (CAA). Failure of perivascular drainage of Aß along cerebrovascular basement membranes contributes to the development of CAA. Mid-life hypercholesterolaemia is a risk factor for the development of AD. Maternal obesity is associated with the development of obesity, hypertension and hypercholesterolaemia in adulthood, suggesting that the risk for AD and CAA may also be influenced by the early-life environment. In the present study, we tested the hypothesis that early-life exposure to a high-fat diet results in changes to the cerebrovasculature and failure of Aß clearance from the brain. We also assessed whether vascular Aß deposition is greater in the brains of aged humans with a history of hyperlipidaemia, compared to age-matched controls with normal lipidaemia. Using a mouse model of maternal obesity, we found that exposure to a high-fat diet during gestation and lactation induced changes in multiple components of the neurovascular unit, including a down-regulation in collagen IV, fibronectin and apolipoprotein E, an up-regulation in markers of astrocytes and perivascular macrophages and altered blood vessel morphology in the brains of adult mice. Sustained high-fat diet over the entire lifespan resulted in additional decreases in levels of pericytes and impaired perivascular clearance of Aß from the brain. In humans, vascular Aß load was significantly increased in the brains of aged individuals with a history of hypercholesterolaemia. These results support a critical role for early dietary influence on the brain vasculature across the lifespan, with consequences for the development of age-related cerebrovascular and neurodegenerative diseases.
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Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
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Encéfalo
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Artérias Cerebrais
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Peptídeos beta-Amiloides
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Angiopatia Amiloide Cerebral
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Fenômenos Fisiológicos da Nutrição Materna
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Doença de Alzheimer
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Dieta Hiperlipídica
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Fenômenos Fisiológicos da Nutrição Animal
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Obesidade
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article