Targeting tumor necrosis factor alpha for Alzheimer’s disease

Boris Decourt, Debomoy Lahiri, Marwan N. Sabbagh

Research output: Contribution to journalReview article

32 Citations (Scopus)

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

Fingerprint

Alzheimer Disease
Tumor Necrosis Factor-alpha
Pharmacology
Pathology
Inflammation
tau Proteins
Clinical Trials, Phase I
Amyloid beta-Peptides
Cognition
Dementia
Rodentia
Anti-Inflammatory Agents
Cytokines
Brain
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Targeting tumor necrosis factor alpha for Alzheimer’s disease. / Decourt, Boris; Lahiri, Debomoy; Sabbagh, Marwan N.

In: Current Alzheimer Research, Vol. 14, No. 4, 01.04.2017, p. 412-425.

Research output: Contribution to journalReview article

Decourt, Boris ; Lahiri, Debomoy ; Sabbagh, Marwan N. / Targeting tumor necrosis factor alpha for Alzheimer’s disease. In: Current Alzheimer Research. 2017 ; Vol. 14, No. 4. pp. 412-425.
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