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Aging Cell. 2018 Oct;17(5):e12818. doi: 10.1111/acel.12818. Epub 2018 Aug 6.

High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model.

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The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel.
The Advanced Technology Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
Pharmacology Division, Faculty of Medicine, The Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Psychology, Bar Ilan University, Ramat-Gan, Israel.
The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, New York.
The Interdisciplinary Center, Herzliya, Israel.


Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood-brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high-fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content. In terms of behavior, Tg2576 HFD mice were less active and more anxious, but had better learning in the Morris Water Maze compared to Tg2576 on regular diet. HFD had no effect on the level of amyloid beta 1-42 in the cortex of Tg2576 mice, but increased the transcription level of insulin receptor in the hippocampus. Tg2576 mice on regular diet demonstrated more BBB disruption at 8 and 12 months accompanied by larger lateral ventricles volume in contrast to Tg2576 HFD mice, whose BBB leakage and ventricular volume were similar to wild-type (WT) mice. Our results suggest that in AD, HFD may promote better cognitive function through improvements of BBB function and of brain atrophy but not of amyloid beta levels. Lipid metabolism in the CNS and peripheral tissues and brain insulin signaling may underlie this protection.


Alzheimer’s disease; MRI; Tg2576 mice; amyloid beta; blood-brain barrier; cholesterol; high-fat diet; insulin resistance

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