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

Abstract

SummaryThere 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.

The Role ofAnethum graveolensL. (Dill) in the Management of Diabetes

“…Glycation reaction leads to alteration in the structure and function of biomolecules particularly proteins. AGE formation is known as a key element in diabetes complications [41–46]. …”

Biotic/Abiotic Stress-Driven Alzheimer's Disease

“…Trauma can significantly increase expression of the alarmin HMBG1 (Horst et al, 2016), which in turn activates an inflammatory cascade by stimulating multiple receptors including RAGE and TLR4 (Mazarati et al, 2011). A recent study showed that AD-like model mice, on a diet enriched in AGEs due to irradiation, exhibit significant memory dysfunction, accompanied with the hippocampal deposition of insoluble Aβ42 fragment and AGEs (Lubitz et al, 2016). This latter finding was consistent with the notion that Aβ can activate microglia and induce neurotoxicity by RAGE binding (Yan et al, 1996).…”

Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor–Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products

“…The diet containing a regular AGE product content was prepared without exposure to heat, while the diet with a high AGE product content consisted of the same chow exposed to gamma irradiation from a cobalt-60 source as per standard procedure. Both diets were therefore nutritionally equivalent and differed only in the content of AGE products (for a more detail, see [38]). Diets were pelleted by the manufacturer and kept at room temperature.…”

“…After evaluation of their cognitive functions at 11 months of age, animals were anesthetized with isoflurane (Baxter Healthcare Corp., Deerfield, IL, USA) and sacrificed by decapitation. The right brain hemisphere was fixed and then used for histological/morphological analyses (the results will be published separately along with those of behavioral testing using the Morris water maze [38]). The left hemisphere was rapidly frozen in liquid nitrogen, stored at -80°C and then used for neurochemical analyses.…”