TY - JOUR
T1 - High-fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model
AU - Elhaik Goldman, Shirin
AU - Goez, David
AU - Last, David
AU - Naor, Sharone
AU - Liraz Zaltsman, Sigal
AU - Sharvit-Ginon, Inbal
AU - Atrakchi-Baranes, Dana
AU - Shemesh, Chen
AU - Twitto-Greenberg, Rachel
AU - Tsach, Shoval
AU - Lotan, Roni
AU - Leikin-Frenkel, Alicia
AU - Shish, Aviv
AU - Mardor, Yael
AU - Schnaider Beeri, Michal
AU - Cooper, Itzik
N1 - Publisher Copyright:
© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - MRI
KW - Tg2576 mice
KW - amyloid beta
KW - blood–brain barrier
KW - cholesterol
KW - high-fat diet
KW - insulin resistance
UR - http://www.scopus.com/inward/record.url?scp=85053890305&partnerID=8YFLogxK
U2 - 10.1111/acel.12818
DO - 10.1111/acel.12818
M3 - Article
C2 - 30079520
AN - SCOPUS:85053890305
SN - 1474-9718
VL - 17
JO - Aging Cell
JF - Aging Cell
IS - 5
M1 - e12818
ER -