THE ALZHEIMER'S PLAQUES, TANGLES AND MEMORY DEFICITS MAY HAVE A COMMON ORIGIN - PART II: THERAPEUTIC RATIONALE

Ming Chen

Department of Pharmacology and Therapeutics, University of South Florida , College of Medicine, Tampa, Florida 33612, and Medical Research Service (151), Bay Pines VA Medical Center, St. Petersburg, Florida 33744

Received 5/15/98 Accepted 5/24/98

5. REFERENCES

1. Selkoe, D. J. Amyloid beta-protein and the genetics of Alzheimer's disease. J Biol Chem 271, 18295-18298 (1996)

2. Beyreuther, K. and Masters, C. Serpents on the road to dementia and death. Nature Med 3, 723-725 (1997)

3. Yankner, B. A. Mechanisms of neuronal degeneration in Alzheimer's disease. Neuron 16, 921-932 (1996)

4. Trojanowski, J. Q. and Lee, V. M-Y. Phosphorylation of paired helical filament tau in Alzheimer's disease neurofibrillary lession: focusing on phosphatases. FASEB J 9, 1570-1576 (1995)

5. Khachaturian Z S. Calcium hypothesis of Alzheimer's disease and brain aging. Ann N Y Acad Sci 747, 1-11 (1994)

6. Chen, M. Alzheimer's a -secretase may be a calcium-dependent protease. FEBS Lett 417, 163-167 (1997)

7. Chen, M. Is Alzheimer's disease associated with a decreased intracellular level of calcium? Front Biosci 3, let1-let2 (1998)(www.bioscience.org/v3/let/chen/list.htm)

8. Chen, M. The Alzheimer's plaques, tangles and memory deficits may have a common origin (Part I: a calcium deficit hypothesis). Front Biosci 3, a27-31 (1998) (http://www.bioscien.org/v3/a/chen/list.htm)

9. Kandel, E. R. and Schwartz, J. H. Principles of Neural Science 3rd edn. Simon & Schuester, New York (1991)

10. Greenberg, B. D, Savage, M. J, Howland, D. S. Ali, S. M. Siedlak, S. L. Perry, G. Siman, R. Scott, R. W. APP transgenesis: approaches toward the development of animal models for Alzheimer disease neuropathology. Neurobiol Aging 17, 153-171 (1995)

11. Price, D. L. and Sisodia, S. S. Cellular and molecular biology of Alzheimer's disease and animal models. Ann Rev Med 45, 435-446 (1994)

12. Games, D. Adams, D, Alessandrini, R. Barbour, R. Berthelette, P. Blackwell, C. Carr, T. Clemens, J. Donaldson, T. Gillespie, F. et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373, 523-527 (1995)

13. Hsiao, K. Chapman, P. Nilsen, S. Eckman, C. Harigaya, Y. Younkin, S. Yang, F. and Cole, G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99-102 (1996)

14. Lannfelt, L. Basun, H. Wahlund, L-O. Rowe, B. A. and Wagner, S. L. Decreased a -secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer's disease. Nature Med 1, 829-832 (1995)

15. Suzuki, K. Sorimachi, H. Yoshizawa, T. Kinbara, K. and Ishiura, S. Calpain: novel family members, activation, and physiologic function. Biol Chem Hoppe-Seyler 376, 523-529 (1995)

16. Terry, R. D. Masliah, E. Salmon, D. P. Butters, N. DeTeresa, R. Hill, R. Hansen, L. A. and Katzman, R. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30, 572-580 (1990)

17. Alonso, A. Grundke-Iqbal, I. and Iqbal K. Alzhiemer's disease hyperphosphorylated tau sequesters normal tau into tangles and disassembles microtubules. Nature Med 1996; 2:783-787.

18. Snowdon, D. A. Greiner, L. H. Mortimer, J. A. Riley, K. P. Greiner, P. A. and Markesbery, W. R. Brain infarction and the clinical expression of Alzheimer disease. JAMA 277, 813-817 (1997)

19. Gomez-Isla, T, Wasco, W. Pettingell, W. P. Gurubhagavatula, S. Schmidt, S. D. Jondro, P. D. McNamara, W. B. Rodes, L. A. DiBlasi, T. Growdon, W. B. Seubert, P. Schenk, D. Growdon, J. H. Hyman, B. T. and Tanzi, R. E. A novel presenilin-1 mutation: increase beta-amyloid and neurofibrillary changes. Ann Neurol 41, 809-813 (1997)

20. Wolozin, B. Iwasaki, K. Vito, P. Ganjei, J. K. Lacana, E. Sunderland, T. Zhao, B. Kusiak, J. W. Wasco, W. and D'Aamio, L. Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 274, 1710-1712 (1996)

21. Weidemann, A. Paliga, K. Durrwang, U. Czech, C. Evin, G. Masters, C. L. and Beyreuther, K. Formation of stable complexes between two Alzheimer's disease gene products: presenilin-2 and beta-amyloid precursor protein. Nature Med 3, 328-332 (19971)

22. Dewji, N. N. and Singer, S. J. Specific transcellular binding between membrane proteins crucial to Alzheimer disease. Proc Natl Acad Sci USA 93, 12575-12580 (1996)

23. Xia, W. Zhang, J, Perez, R. Koo, E. H. and Selkoe, D. J. Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease. Proc Natl Acad Sci USA 94, 8208-8213 (1997)

24. Haass, C. Lemere, C. A. Capell, A. Citron, M. Seubert, P. Schenk, D. Lannfelt, L. and Selkoe, D. J. The Swedish mutation causes early-onset Alzheimer's disease by ß-secretase cleavage within the secretory pathway. Nature Med 1, 1291-1296 (1995)

25. Jeffery, P. Greenfield, G. K. and Xu, H. Cellular and molecular basis of ß-amyloid precursor protein metabolism. Front Biosci 3, d399-407 (1998)

26. Scheuner, D. Eckman, C. Jensen, M. Song, X. Citron, M. Suzuki, N. Bird, T. D. Hardy, J. Hutton, M. Kukull, W. Larson, E. Levy-Lahad, E. Vitanen, M. Peskind, E. Poorkaj, P. Schellenberg, G. Tanzi, R. Wasco, W. Lannfelt, L. Selkoe, D. and Younkin, S. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Med 2, 864-870 (1996)

27. Duff, K. Eckman, C. Zehr, C. Yu, X. Prada, C. M. Pereztur, J. Hutton, M. Buee, L. Harigaya, Y. Yager, D. Morgan, D. et al.. Increased amyloid-ß(42/43) in brains of mice expressing mutant presenilin 1. Nature 383, 710-713 (1996)

28. Citron, M. Westaway, D. Xia, W. M. Carlson, G. Diehl, T. Levesque, G. Johnson-Wood, K. Lee, M. Seubert, P. Davis, A. Kholodenko, D. Motter, R. Sherrington, R. Perry, B. Yao, H. Strome, R. Lieberburg, I. Rommens, J. Kim, S. Schenk, D. Fraser, P. St. George Hyslop, P. and Selkoe, D. J. Mutant presenlins of Alzheimer's disease increase production of 42-residue amyloid ß-protein in both transfected cells and transgenic mice. Nature Med 3, 67-72 (1997)

29. Marx, J. Dissecting how presenilins function-and malfunction. Science 274, 1838-1840 (1996)

30. Rowland, L. P. Eds. Merritt's Textbook of Neurology 9th edn. Williams & Wilkins, Baltimore (1995)

31. Saito K-I, Elce J S, Hamos J E, Nixon R A. Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. Proc Natl Acad Sci USA 90, 2628-2632 (1993).

32. Schmage, N. and Bergener, M. Global rating, symptoms, behavior, and cognitive performance as indicators of efficacy in clinical studies with nimodipine in elderly patients with cognitive impairment syndromes. Intl. Psychogeriatrics 4 Suppl 1, 89-99 (1992)

33. Behan, D. P. Heinrichs, S. C. Troncoso, J. C. Liu, X. J. Kawas, C. H. Ling, N. De Souza, E. B. Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease. Nature 378, 284-287 (1995)

34. Nitsch, R. M. Wurtman, R. J. and Growdon, J. H. Regulation of APP processing potential for the therapeutic reduction of brain amyloid burden. Ann N Y Acad Sci 777, 175-182 (1996)

35. Buxbaum, J. D. Ruefli, A. A. Parker, C. A. Cypess, A. M. and Greengard, P. Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C- independent manner. Proc Natl Acad Sci USA 91, 4489-4493 (1994)

36. Marx, J. Searching for drugs that combat Alzheimer's. Science 273, 50-53 (1996)

37. Kovacs, D. M. Fausett, H. J. Page, K. J. Kim, T.-W. Moir, R. D. Merriam, D. E. Hollister, R. D. Hallmark, O. G. Mancini, R. Felsenstein, K. M. Hyman, B. T. Tanzi, R. E. and Wasco, W. Alzheimer-assoicated presenilin 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammlian cells. Nature Med 2, 224-229 (1996)