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 hallmarks
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.
Keywords: Alzheimer’s disease, BACE1, etanercept, inflammation, neuroinflammation, thalidomide, TNF-α.
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