Alzheimer’s disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hall-marks of AD are extracellular deposits of amyloid beta (Aβ) peptides assembled in plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo. Interestingly, preventive and intervention anti-inflammatory strategies demonstrated a reduction in brain pathology and an amelioration of cognitive function in rodent models of AD. Phase I and IIa clinical trials suggest that TNF-α inhibitors might slow down cognitive decline and improve daily activities in AD patients. In the present review, we summarize the evidence pointing towards a beneficial role of anti-TNF-α therapies to prevent or slow the progression of AD. We also present possible physical and pharmacological interventions to modulate TNF-α signaling in AD subjects along with their limitations.
|Original language||English (US)|
|Number of pages||14|
|Journal||Current Alzheimer research|
|State||Published - Apr 1 2017|
- Alzheimer’s disease
ASJC Scopus subject areas
- Clinical Neurology