The differential effects of fatty acids on enterocytic abundance of amyloid-beta

Abstract

BackgroundConsumption of a Western-styled diet enriched in saturated fatty acids (SFA) relative to polyunsaturated fatty acids is positively associated with risk for Alzheimer’s disease. Whilst potential causal mechanism are unclear, there is increasing evidence that chronic ingestion of SFA enriched diets promote increase the plasma levels of lipoprotein-associated amyloid-β (Aβ). However, the effects of dietary mono- and poly-unsaturated fats (MUFA/PUFA) on nascent lipoprotein Aβ abundance have not been previously reported.MethodsWild-type C57BL/6 J mice were maintained on low-fat control chow (LF) or diets enriched in either SFA, MUFA, or PUFA for 9 months. Enterocytic abundance of Aβ was determined with quantitative immunofluorescent microscopy and plasma Aβ was measured by ELISA.ResultsThe chronic ingestion of SFA-enriched diet increased the enterocytic abundance and plasma concentration of Aβ compared to LF control mice. The mice maintained on MUFA or PUFA diet showed comparable enterocytic and plasma Aβ levels to the LF control mice.ConclusionsThe data indicates that a diet enriched in SFA significantly increases the enterocytic Aβ production and secretion into the circulation, whilst MUFA and PUFA enriched diet do not exert such effects.

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

“…The Gram-negative bacteria are the main producers of Aβ prion-like proteins (i.e., a-synuclein) and lipopolysaccharides (LPS), and select pro-inflammatory TLR4. Among the Gram-negative bacteria, B. subtilis and E. choli produce large amounts of Aβ and LPS [8,14,16,17].…”

“…Several studies have shown that, besides the brain, the microbiota-gut system is a site of Aβ production, and that the enterocytes contain substantial amounts of Aβ [40,48,49], and that diet and intestinal microbiota regulate the Aβ presence in the gut epithelium [17,25]. Gramnegative bacteria are a significant source of Aβ and of LPS, and the increased levels of these molecules found in AD brain plaques were related to dysbiosis.…”

“…Two different routes have been considered. The first begins from the enterocytes, where Aβ and LPS are integrated in CM-containing ApoE proteins [12,17,48] and, through the blood stream, they reach the brain [45,55]. For Aβ, the following second route of diffusion has been postulated: because of its prion-like proteins, Aβ could arrive to the brain via neuron-to-neuron retrograde transport from the ENS to the brain through the vagus nerve [25,56,57].…”

Modelling bioactivities of combinations of whole extracts of edibles with a simplified theoretical framework reveals the statistical role of molecular diversity and system complexity in their mode of action and their nearly certain safety

“…Many studies on the relationship between food and health focus on specific nutrients, for instance on saturated and unsaturated fat, fibers, etc. [28]. The latter could well be surrogate markers of nutritional diversity.…”

Amyloid beta emerges from below the neck to disable the brain

“…Pharmacological reduction of Aβ levels in the blood of wild-type mice by peripheral administration of a drug impermeable to the blood–brain barrier was linked to reduced Aβ levels in the brain [ 9 ]. Dietary fatty acids can also modulate plasma Aβ levels in wild-type mice [ 10 ]. These findings provide evidence that Aβ levels in blood can be modulated; however, further studies are needed to establish whether or not peripherally targeted strategies to reduce Aβ would be beneficial for brain function and cognition in the context of Alzheimer disease.…”