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Maternal obesity is associated with increased risk of diabetes,cardiovascular disease and hypertension in adult offspring. Midlifehypercholesterolemia and hypertension are risk factors for Alzheimer's disease,suggesting that the ageing brain may be impacted by early life environment. Wefound that exposure to a high fat diet during gestation and lactation inducedchanges in multiple components of the neurovascular unit, including adownregulation in apolipoprotein E and fibronectin, an upregulation in markersof astrocytes and perivascular macrophages and altered blood vessel morphologyin the brains of adult mice. Feeding of high fat diet after weaning increasedlipid droplets in the brain and influenced the fatty acid composition ofphosphatidylcholine and phosphatidylethanolamine species, but did not affectthe neurovascular unit. Sustained high fat diet over the entire lifespanresulted in additional decreases in levels of pericytes and collagen IV,changes in phospholipid composition and impaired perivascular clearance ofBeta-amyloid (A-Beta) from the brain. In humans, vascular A-Beta load wassignificantly increased in the brains of aged individuals with a history ofhypercholesterolemia. These results support a critical role for early dietaryinfluence on the brain vasculature across the lifespan, with consequences forthe development of age-related cerebrovascular and neurodegenerative diseases.

Impact of maternal high fat on neurovascular unit of adult offspring