The endotoxin hypothesis of Alzheimer’s disease (AD) proposes that lipopolysaccharide (LPS), a component of Gram-negative bacteria, contributes to AD pathogenesis by increasing inflammation and neurodegeneration. Elevated LPS levels in the blood and brain of AD patients are associated with increased amyloid beta (Aβ) and tau pathology, microglial activation, and synaptic loss. LPS induces Aβ aggregation, tau phosphorylation, and neuroinflammation, and can cause cognitive dysfunction and memory loss in animal models. LPS also promotes microglial activation and neurotoxicity, and may contribute to synaptic loss and neuronal death. The hypothesis suggests that peripheral infections, gut dysfunction, or bacterial infections can elevate LPS levels, which in turn promote AD pathology. Evidence includes increased LPS levels in AD patients, LPS-induced Aβ and tau pathology, and LPS-induced neuroinflammation. However, the hypothesis is not universally accepted, as LPS levels are also elevated in other conditions, and some studies suggest that LPS may have neuroprotective effects. Potential treatments include reducing infections, modifying the gut microbiome, reducing gut permeability, and blocking LPS response. The endotoxin hypothesis is supported by multiple lines of evidence, but further research is needed to confirm its validity and to develop effective treatments for AD.The endotoxin hypothesis of Alzheimer’s disease (AD) proposes that lipopolysaccharide (LPS), a component of Gram-negative bacteria, contributes to AD pathogenesis by increasing inflammation and neurodegeneration. Elevated LPS levels in the blood and brain of AD patients are associated with increased amyloid beta (Aβ) and tau pathology, microglial activation, and synaptic loss. LPS induces Aβ aggregation, tau phosphorylation, and neuroinflammation, and can cause cognitive dysfunction and memory loss in animal models. LPS also promotes microglial activation and neurotoxicity, and may contribute to synaptic loss and neuronal death. The hypothesis suggests that peripheral infections, gut dysfunction, or bacterial infections can elevate LPS levels, which in turn promote AD pathology. Evidence includes increased LPS levels in AD patients, LPS-induced Aβ and tau pathology, and LPS-induced neuroinflammation. However, the hypothesis is not universally accepted, as LPS levels are also elevated in other conditions, and some studies suggest that LPS may have neuroprotective effects. Potential treatments include reducing infections, modifying the gut microbiome, reducing gut permeability, and blocking LPS response. The endotoxin hypothesis is supported by multiple lines of evidence, but further research is needed to confirm its validity and to develop effective treatments for AD.