Alzheimer’s disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of daily living activities, and a variety of neuropsychiatric symptoms and behavioral disturbances.

Increasing evidence shows that neurotoxicity is mediated by CNS inflammatory processes, which involve activation of the microglia by the amyloid-beta, leading to the release of proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Neurotoxic processes mediated by these cytokines may include direct neuronal death by enhancement of apoptosis, decreased synaptic function, and inhibition of hippocampal neurogenesis.1

Rosiglitazone is used in some studies for improving the symptoms of Alzheimer’s disease but there is controversy about its mechanism of action.2

There is evidence that shows the effect of rosiglitazone in reducing IL-6.3 Although a study has shown that rosiglitazone cannot reduce IL-6,4 it seems that this study was not maintained long enough to determine this effect.

In addition, a study showed that poor sleep is associated with higher interleukin-6 in older caregivers of people with Alzheimer’s disease.5

According to aforementioned studies, we hypothesize that one of the mechanisms of action of rosiglitazone in ameliorating Alzheimer’s disease is reducing IL-6. Moreover, it seems that this drug can improve the sleep of people with Alzheimer’s disease.

Prescribing other IL-6 reducers as clenbuterol may be a good treatment for Alzheimer’s disease. On the other hand, TNF-alpha antagonists, like thalidomide, infliximab, etanercept, and adalimumab, may be effective in Alzheimer’s disease.

Surely, clinical trials are needed to validate our hypothesis.