title: Targeting Tumor Necrosis Factor Alpha for Alzheimer's Disease.
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 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.
authors.affiliation: Banner Sun Health Research Institute, 10515 W. Santa Fe Dr., Sun City AZ 85351, United States.
authors.forename: Boris
authors.initials: B
authors.lastname: Decourt
authors.affiliation: Institute of Psychiatry Research, Department of Psychiatry, School of Medicine, Indiana University-Purdue University, Indianapolis, IN, United States.
authors.forename: Debomoy K
authors.initials: DK
authors.lastname: Lahiri
authors.affiliation: Alzheimer's and Memory Disorders Division, Barrow Neurological Institute, 240 West Thomas, Ste 301, Phoenix, AZ 85013, United States.
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Alzheimer's disease; BACE1; TNF-alpha.; etanercept; inflammation; neuroinflammation; thalidomide