Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Reducing Dietary Lipopolysaccharides to Slow Progression of Cognitive Impairment and Alzheimer’s Disease

Version 1 : Received: 25 March 2024 / Approved: 26 March 2024 / Online: 26 March 2024 (06:52:42 CET)

How to cite: Blake, S.M.; Baroni, L.; Blake, C.P.; Harding, T.; Piboolnurak, P.; Harding, M.; Grant, W.B. Reducing Dietary Lipopolysaccharides to Slow Progression of Cognitive Impairment and Alzheimer’s Disease. Preprints 2024, 2024031549. https://doi.org/10.20944/preprints202403.1549.v1 Blake, S.M.; Baroni, L.; Blake, C.P.; Harding, T.; Piboolnurak, P.; Harding, M.; Grant, W.B. Reducing Dietary Lipopolysaccharides to Slow Progression of Cognitive Impairment and Alzheimer’s Disease. Preprints 2024, 2024031549. https://doi.org/10.20944/preprints202403.1549.v1

Abstract

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

Keywords

Alzheimer’s disease; cognitive impairment; cytokines; dairy; dementia; diet; endotoxin; inflammation; lipopolysaccharides; meat

Subject

Public Health and Healthcare, Health Policy and Services

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