Targeting tumor necrosis factor alpha for Alzheimer’s disease

Boris Decourt, Debomoy Lahiri, Marwan N. Sabbagh

Research output: Contribution to journalReview article

48 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)412-425
Number of pages14
JournalCurrent Alzheimer Research
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2017

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Keywords

  • Alzheimer’s disease
  • BACE1
  • Etanercept
  • Inflammation
  • Neuroinflammation
  • Thalidomide
  • TNF-α

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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