title: High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model.
abstract: There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42 , AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD-like model mice on high-AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood-brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle-linked disease epidemic.
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Lubitz
authors.affiliation: Department of Biochemistry and Brain Pathophysiology, National Institute of Mental Health, Topolova 748, Klecany, 250 67, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Ricny
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Atrakchi-Baranes
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Shemesh
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Kravitz
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Liraz-Zaltsman
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Maksin-Matveev
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.
authors.forename: Itzik
authors.initials: I
authors.lastname: Cooper
authors.affiliation: Department of Internal Medicine D and Hypertension Unit, Sheba Medical Center, Ramat Gan, 52621, Israel.
authors.forename: Avshalom
authors.initials: A
authors.lastname: Leibowitz
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, 10029, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Uribarri
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, 10029, USA.
authors.forename: James
authors.initials: J
authors.lastname: Schmeidler
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, 10029, USA.
authors.forename: Weijing
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Biochemistry and Brain Pathophysiology, National Institute of Mental Health, Topolova 748, Klecany, 250 67, Czech Republic.
authors.forename: Zdena
authors.initials: Z
authors.lastname: Kristofikova
authors.affiliation: Department of Biochemistry and Brain Pathophysiology, National Institute of Mental Health, Topolova 748, Klecany, 250 67, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ripova
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mt Sinai, New York, NY, 10029, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.affiliation: The Joseph Sagol Neuroscience Center Tel Hashomer, Ramat Gan, 52621, Israel.|Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, 10029, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Schnaider-Beeri
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D065853:Spatial Learning / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced
keywords: Alzheimer's disease; Aβ; Tg2576; advanced glycation end product; blood-brain barrier; receptor for advanced glycation end product