The endotoxin hypothesis of Alzheimer's disease.
Mol Neurodegener
; 19(1): 30, 2024 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-38561809
ABSTRACT
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 Aß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Neurodegener
/
Mol. neurodegener
/
Molecular neurodegeneration
Year:
2024
Document type:
Article
Affiliation country:
Reino Unido
Country of publication:
Reino Unido