Ramos EM, Lin MT, Larson EB, Maezawa I, Tseng LH, Edwards KL, Schellenberg GD, Hansen JA, Kukull WA, Jin LW. Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch Neurol. 2006 Aug;63(8):1165-9. PubMed.
Recommends
Please login to recommend the paper.
Comments
This article, resulting from the collaboration between both the University of Washington and the University of California, Davis, provides robust new evidence that further implicates excess TNFα in the pathogenesis of Alzheimer disease. This article joins an increasing body of evidence that began in the early 1990s, with the work of Howard Fillit (Fillit et al, 1991), and the multiple publications from the Vancouver group led by McGeers (Klegeris et al., 1997). It has continued with multiple publications in 2006 (see references), which suggest that TNFα plays a central role in the pathogenesis of Alzheimer disease. A search in Google Scholar of "TNF Alzheimer's" now yields over 4,000 citations.
Ramos and his co-authors conclude: "The data support that therapeutic strategies designed to reduce TNFα protein production or activity might be a valuable treatment for AD." There is an urgent need for the Alzheimer research community to take note of these findings and initiate further study of this highly promising approach to Alzheimer disease treatment. This is particularly true in view of the availability of a potent and selective biologic inhibitor of TNFα, etanercept, and a new method of perispinal delivery which may enhance its therapeutic activity for CNS applications (see Tobinick et al., 2006). (Please, of course, see my accompanying disclosure.)
References:
Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G. Elevated circulating tumor necrosis factor levels in Alzheimer's disease. Neurosci Lett. 1991 Aug 19;129(2):318-20. PubMed.
Klegeris A, Walker DG, McGeer PL. Interaction of Alzheimer beta-amyloid peptide with the human monocytic cell line THP-1 results in a protein kinase C-dependent secretion of tumor necrosis factor-alpha. Brain Res. 1997 Jan 30;747(1):114-21. PubMed.
Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed. 2006;8(2):25. PubMed.
Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, Sonobe Y, Mizuno T, Suzumura A. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem. 2006 Jul 28;281(30):21362-8. PubMed.
Ralay Ranaivo H, Craft JM, Hu W, Guo L, Wing LK, Van Eldik LJ, Watterson DM. Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration. J Neurosci. 2006 Jan 11;26(2):662-70. PubMed.
Ramos EM, Lin MT, Larson EB, Maezawa I, Tseng LH, Edwards KL, Schellenberg GD, Hansen JA, Kukull WA, Jin LW. Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch Neurol. 2006 Aug;63(8):1165-9. PubMed.
Même W, Calvo CF, Froger N, Ezan P, Amigou E, Koulakoff A, Giaume C. Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by beta-amyloid. FASEB J. 2006 Mar;20(3):494-6. PubMed.
Lio D, Annoni G, Licastro F, Crivello A, Forte GI, Scola L, Colonna-Romano G, Candore G, Arosio B, Galimberti L, Vergani C, Caruso C. Tumor necrosis factor-alpha -308A/G polymorphism is associated with age at onset of Alzheimer's disease. Mech Ageing Dev. 2006 Jun;127(6):567-71. PubMed.
Craft JM, Watterson DM, Van Eldik LJ. Human amyloid beta-induced neuroinflammation is an early event in neurodegeneration. Glia. 2006 Apr 1;53(5):484-90. PubMed.
Zuliani G, Ranzini M, Guerra G, Rossi L, Munari MR, Zurlo A, Volpato S, Atti AR, Blè A, Fellin R. Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. J Psychiatr Res. 2007 Oct;41(8):686-93. PubMed.
Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed. 2006;8(2):25. PubMed.
Alvarez A, Cacabelos R, Sanpedro C, García-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging. 2007 Apr;28(4):533-6. PubMed.
Make a Comment
To make a comment you must login or register.