The Institute for Neurological Research, a private medical group, inc. has invented and pioneered new therapeutic approaches for a variety of neurological disorders with widespread unmet medical need, including Alzheimer's, dementia, and related memory disorders. Many of these novel methods involve the use of newly available therapeutic molecules which have been developed through the use of biotechnology. Included among these are molecules which inhibit the biologic activity of TNF-alpha. TNF-alpha is a proinflammatory cytokine, a molecule which initiates and amplifies the inflammatory response in the human body. The following are just a small number of the recent scientific studies which have suggested a role for TNF-alpha in mechanisms involved in memory and Alzheimer's, including mechanisms involving amyloid, NMDA, glutamate, and synaptic transmission:

1. Tobinick, E., and Gross, H., Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration. J Neuroinflammation, 2008. 5: p.2. (Download free full-text PDF).
2. Griffin, W.S., Perispinal etanercept: Potential as an Alzheimer therapeutic. J Neuroinflammation, 2008. 5(1): p.3. (Download free full-text PDF).
3. 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.
4. Tobinick, E., Perispinal etanercept for treatment of Alzheimer's Disease. Current Alzheimer Research, 2007. 4(5): p. 550-552.
5. Jekabsone, A., et al., Fibrillar beta-amyloid peptide Abeta1-40 activates microglial proliferation via stimulating TNF-alpha release and H2O2 derived from NADPH oxidase: a cell culture study. J Neuroinflammation, 2006. 3: p. 24.
6. Ramos, E.M., et al., 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.
7. Csiszar, A., et al., Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Am J Pathol, 2007. 170(1): p. 388-98.
8. Stellwagen, D., et al., Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci, 2005. 25(12): p. 3219-28.
9. Lio, D., et al., Tumor necrosis factor-alpha -308A/G polymorphism is associated with age at onset of Alzheimer's disease. Mech Ageing Dev, 2006. 127(6): p. 567-71.
10. Pickering, M., D. Cumiskey, and J.J. O'Connor, Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol, 2005. 90(5): p. 663-70.
11. Mbebi, C., et al., Antibody-bound beta-amyloid precursor protein stimulates the production of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 by cortical neurons. Neurobiol Dis, 2005. 19(1-2): p. 129-41.
12. Laws, S.M., et al., TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels. Hum Mutat, 2005. 26(1): p. 29-35.
13. Floden, A.M., S. Li, and C.K. Combs, Beta-amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor alpha and NMDA receptors. J Neurosci, 2005. 25(10): p. 2566-75.
14. De, A., J.M. Krueger, and S.M. Simasko, Glutamate induces the expression and release of tumor necrosis factor-alpha in cultured hypothalamic cells. Brain Res, 2005 Aug 16: 1053(1-2):54-61.
15. Tarkowski, E., et al., Intrathecal inflammation precedes development of Alzheimer's disease. J Neurol Neurosurg Psychiatry, 2003. 74(9): p. 1200-5.
16. McGeer, E.G. and P.L. McGeer, Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry, 2003. 27(5): p. 741-9.
17. Tarkowski, E., et al., Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull, 2003. 61(3): p. 255-60.
18. Zuliani, G., et al., Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. J Psychiatr Res, 2007 Oct; 41(8): 686-93. Epub 2006 Apr 4.
19. Alvarez, A., et al., Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging, 2007 Apr; 28(4):533-6.
20. Stellwagen, D., Malenka RC, Synaptic scaling mediated by glial TNF-alpha. Nature, 2006 Apr 20; 440(7087):1054-9.


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Copyright ©2007, the Institute for Neurological Research®, a private medical group, inc. The following U.S. patents protect the Institute's inventions: 6015557, 6177077, 6419934, 6419944, 6471961, 6537549, 6982089, 7214658, and other issued and pending patents. The Institute conducts a private medical practice.
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