  Maternal obesity is associated with increased risk of diabetes,
cardiovascular disease and hypertension in adult offspring. Midlife
hypercholesterolemia and hypertension are risk factors for Alzheimer's disease,
suggesting that the ageing brain may be impacted by early life environment. We
found that exposure to a high fat diet during gestation and lactation induced
changes in multiple components of the neurovascular unit, including a
downregulation in apolipoprotein E and fibronectin, an upregulation in markers
of astrocytes and perivascular macrophages and altered blood vessel morphology
in the brains of adult mice. Feeding of high fat diet after weaning increased
lipid droplets in the brain and influenced the fatty acid composition of
phosphatidylcholine and phosphatidylethanolamine species, but did not affect
the neurovascular unit. Sustained high fat diet over the entire lifespan
resulted in additional decreases in levels of pericytes and collagen IV,
changes in phospholipid composition and impaired perivascular clearance of
Beta-amyloid (A-Beta) from the brain. In humans, vascular A-Beta load was
significantly increased in the brains of aged individuals with a history of
hypercholesterolemia. 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.
