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Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring.
J Pathol. 2015 Mar; 235(4):619-31.JP

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) 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 Aβ 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 Aβ clearance from the brain. We also assessed whether vascular Aβ 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 Aβ from the brain. In humans, vascular Aβ 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.

Authors+Show Affiliations

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25345857

Citation

Hawkes, Cheryl A., et al. "Prenatal High-fat Diet Alters the Cerebrovasculature and Clearance of Β-amyloid in Adult Offspring." The Journal of Pathology, vol. 235, no. 4, 2015, pp. 619-31.
Hawkes CA, Gentleman SM, Nicoll JA, et al. Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring. J Pathol. 2015;235(4):619-31.
Hawkes, C. A., Gentleman, S. M., Nicoll, J. A., & Carare, R. O. (2015). Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring. The Journal of Pathology, 235(4), 619-31. https://doi.org/10.1002/path.4468
Hawkes CA, et al. Prenatal High-fat Diet Alters the Cerebrovasculature and Clearance of Β-amyloid in Adult Offspring. J Pathol. 2015;235(4):619-31. PubMed PMID: 25345857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring. AU - Hawkes,Cheryl A, AU - Gentleman,Steve M, AU - Nicoll,James Ar, AU - Carare,Roxana O, Y1 - 2015/01/07/ PY - 2014/04/25/received PY - 2014/10/08/revised PY - 2014/10/12/accepted PY - 2014/10/28/entrez PY - 2014/10/28/pubmed PY - 2015/4/15/medline KW - Alzheimer's disease KW - amyloid KW - brain KW - cerebral vasculature KW - maternal obesity SP - 619 EP - 31 JF - The Journal of pathology JO - J. Pathol. VL - 235 IS - 4 N2 - Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) 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 Aβ 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 Aβ clearance from the brain. We also assessed whether vascular Aβ 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 Aβ from the brain. In humans, vascular Aβ 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. SN - 1096-9896 UR - https://www.unboundmedicine.com/medline/citation/25345857/Prenatal_high_fat_diet_alters_the_cerebrovasculature_and_clearance_of_β_amyloid_in_adult_offspring_ L2 - https://doi.org/10.1002/path.4468 DB - PRIME DP - Unbound Medicine ER -