Session Title: Apolipoprotein-E
SATURATED FATS DISRUPT BLOOD-BRAIN BARRIER INTEGRITY RESULTING IN BLOOD-TO-BRAIN DELIVERY OF LIPOPROTEIN-AMYLOID-BETA; IMPLICATIONS FOR ALZHEIMER'S DISEASE RISK.
R. Takechi1, S. Galloway1, M. Pallebage-Gamarallage1, C. Wellington2, S. Dhaliwal1, R. Johnsen3, J. Mamo1
Some dietary fats are a risk factor for Alzheimer's disease (AD) but the mechanisms for this association are presently unknown. In this study we show in wild-type mice that chronic ingestion of saturated fats (SFA) results in blood-brain barrier (BBB) dysfunction and significant leakage into brain of dietary-derived lipoproteins enriched in amyloid-beta (Ab). In contrast, chronic ingestion of monounsaturated or polyunsaturated fatty acids had no detrimental effect on BBB integrity. Utilizing highly sensitive 3-dimenisional immuno-microscopy, we also show in a murine model of AD, a positive association of intestinal and hepatic derived apolipoprotein B lipoproteins with cerebral amyloid plaque. Collectively, the findings of this study provide a plausible explanation of how dietary fats influence AD risk. Ingestion of saturated fats may enhance peripheral delivery to brain of circulating lipoprotein-Ab and exacerbate the amyloidogenic cascade.