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.
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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.)
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2. Ranaivo, H.R., et al., Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration. J Neurosci, 2006. 26(2): p. 662-70.
3. 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. 63(8): p. 1165-9. Abstract
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6. Craft JM, Watterson DM, Van Eldik LJ. Human amyloid beta-induced neuroinflammation is an early event in neurodegeneration. Glia, 2006. 53(5): p. 484-90. Abstract
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8. 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): p. 25. Abstract
9. Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging, 2006. Abstract