The endoxotin/LPS hypothesis of Alzheimer Disease (AD)
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Nothing surprising here to my readers, but I try to post about such studies since they are usually a marker of an upcoming major shift in medical dogmas. Considering 99%+ of all AD clinical trials over the last 2+ decades have abysmally failed, new ideas about this conditions are urgently needed. The study below is a good summary of the ideas and findings of many other studies, most of which I have posted about on this blog. Namely, endotoxin/LPS is perhaps the major cause of AD, as well as virtually all other neurodegenerative conditions.
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-024-00722-y
“…Lipopolysaccharide (LPS) constitutes much of the surface of Gram-negative bacteria, and if LPS enters the human body or brain can induce inflammation and act as an endotoxin. We outline the hypothesis here that LPS may contribute to the pathophysiology of Alzheimer’s disease (AD) via peripheral infections or gut dysfunction elevating LPS levels in blood and brain, which promotes: amyloid pathology, tau pathology and microglial activation, contributing to the neurodegeneration of AD. The evidence supporting this hypothesis includes: i) blood and brain levels of LPS are elevated in AD patients, ii) AD risk factors increase LPS levels or response, iii) LPS induces Aβ expression, aggregation, inflammation and neurotoxicity, iv) LPS induces TAU phosphorylation, aggregation and spreading, v) LPS induces microglial priming, activation and neurotoxicity, and vi) blood LPS induces loss of synapses, neurons and memory in AD mouse models, and cognitive dysfunction in humans. However, to test the hypothesis, it is necessary to test whether reducing blood LPS reduces AD risk or progression. If the LPS endotoxin hypothesis is correct, then treatments might include: reducing infections, changing gut microbiome, reducing leaky gut, decreasing blood LPS, or blocking LPS response.”