High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

Irit Lubitz, Jan Ricny, Dana Atrakchi-Baranes, Chen Shemesh, Efrat Kravitz, Sigal Liraz-Zaltsman, Anna Maksin-Matveev, Itzik Cooper, Avshalom Leibowitz, Jaime Uribarri, James Schmeidler, Weijing Cai, Zdena Kristofikova, Daniela Ripova, Derek Leroith, Michal Schnaider-Beeri

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalAging Cell
Volume15
Issue number2
DOIs
StatePublished - 1 Apr 2016

Keywords

  • Alzheimer's disease
  • Tg2576
  • advanced glycation end product
  • blood-brain barrier
  • receptor for advanced glycation end product

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