Pathogenesis and Disease-modifying Therapy in Alzheimer's Disease: The Flat Line of Progress

Archives of Medical Research

Volumn 43, Issue 8, 2012, Pages 694-698

  Castellani, Rudy J ^a   Perry, George ^b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b University of San Antonio   (United States)

Author keywords

Alzheimer disease; Amyloid ; Mitochondria; Oxidative stress; Tau; Therapy

Indexed keywords

AMYLOID BETA PROTEIN; TAU PROTEIN;

ALZHEIMER DISEASE; AUTOPHAGY; DIET; ENERGY METABOLISM; ENVIRONMENTAL FACTOR; HUMAN; MITOCHONDRION; OXIDATIVE STRESS; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; REVIEW;

EID: 84871660406     PISSN: 01884409     EISSN: 18735487     Source Type: Journal    
DOI: 10.1016/j.arcmed.2012.09.009     Document Type: Review

References (44)

1. Castellani R.J., Smith M.A. Compounding artefacts with uncertainty, and an amyloid cascade hypothesis that is 'too big to fail'. J Pathol 2011, 224:147-152.
2. Castellani R.J., Lee H.G., Zhu X., et al. Alzheimer disease pathology as a host response. J Neuropathol Exp Neurol 2008, 67:523-531.
3. Castellani R.J., Lee H.G., Siedlak S.L., et al. Reexamining Alzheimer's disease: evidence for a protective role for amyloid-beta protein precursor and amyloid-beta. J Alzheimers Dis 2009, 18:447-452.
4. Castellani R.J., Nunomura A., Rolston R.K., et al. Sublethal RNA oxidation as a mechanism for neurodegenerative disease. Int J Mol Sci 2008, 9:789-806.
5. Nunomura A., Hofer T., Moreira P.I., et al. RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathol 2009, 118:151-166.
6. Longo F.M., Yang T., Knowles J.K., et al. Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms. Curr Alzheimer Res 2007, 4:503-506.
7. Castellani R., Hirai K., Aliev G., et al. Role of mitochondrial dysfunction in Alzheimer's disease. J Neurosci Res 2002, 70:357-360.
8. Tanzi R.E. The synaptic Abeta hypothesis of Alzheimer disease. Nat Neurosci 2005, 8:977-979.
9. Barnett A., Brewer G.J. Autophagy in aging and Alzheimer's disease: pathologic or protective?. J Alzheimers Dis 2011, 25:385-394.
10. Hardy J.A., Higgins G.A. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992, 256:184-185.
11. Giannakopoulos P., Herrmann F.R., Bussiere T., et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003, 60:1495-1500.
12. Nelson P.T., Braak H., Markesbery W.R. Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol 2009, 68:1-14.
13. Arnold S.E., Hyman B.T., Flory J., et al. The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex 1991, 1:103-116.
14. Arriagada P.V., Growdon J.H., Hedley-Whyte E.T., et al. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992, 42:631-639.
15. Berg L., McKeel D.W., Miller J.P., et al. Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 1998, 55:326-335.
16. Bierer L.M., Hof P.R., Purohit D.P., et al. Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease. Arch Neurol 1995, 52:81-88.
17. Benilova I., Karran E., De Strooper B. The toxic Abeta oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci 2012, 15:349-357.
18. St George-Hyslop P.H., Haines J.L., Farrer L.A., et al. Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature 1990, 347:194-197.
19. Nussbaum J.M., Schilling S., Cynis H., et al. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-beta. Nature 2012, 485:651-655.
20. Clavaguera F., Bolmont T., Crowther R.A., et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 2009, 11:909-913.
21. Pritchard S.M., Dolan P.J., Vitkus A., et al. The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics. J Cell Mol Med 2011, 15:1621-1635.
22. Galimberti D., Scarpini E. Clinical phenotypes and genetic biomarkers of FTLD. J Neural Transm 2012, 119:851-860.
23. Lewis J., Dickson D.W., Lin W.L., et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001, 293:1487-1491.
24. Huebner T.S.J., Mehta R., Castellani R.J. Neocortical amyloid-β and tau pathology in patients with cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2012, 71:554.
25. Braak H., Thal D.R., Ghebremedhin E., et al. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011, 70:960-969.
26. Nelson P.T., Alafuzoff I., Bigio E.H., et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 2012, 71:362-381.
27. Nunomura A., Castellani R.J., Zhu X., et al. Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 2006, 65:631-641.
28. Halliwell B., Lee C.Y. Using isoprostanes as biomarkers of oxidative stress: some rarely considered issues. Antioxid Redox Signal 2010, 13:145-156.
29. Smith M.A., Sayre L.M., Vitek M.P., et al. Early AGEing and Alzheimer's. Nature 1995, 374:316.
30. Castellani R.J., Siedlak S.L., Perry G., et al. Sequestration of iron by Lewy bodies in Parkinson's disease. Acta Neuropathol 2000, 100:111-114.
31. Castellani R.J., Smith M.A., Nunomura A., et al. Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?. Free Radic Biol Med 1999, 26:1508-1512.
32. Smith M.A., Taneda S., Richey P.L., et al. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA 1994, 91:5710-5714.
33. Sayre L.M., Zelasko D.A., Harris P.L., et al. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. J Neurochem 1997, 68:2092-2097.
34. Perry G., Cash A.D., Smith M.A. Alzheimer disease and oxidative stress. J Biomed Biotechnol 2002, 2:120-123.
35. Shah R.S., Lee H.G., Xiongwei Z., et al. Current approaches in the treatment of Alzheimer's disease. Biomed Pharmacother 2008, 62:199-207.
36. Wang X., Su B., Lee H.G., et al. Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 2009, 29:9090-9103.
37. Wang X., Su B., Liu W., et al. DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson's disease. Aging Cell 2011, 10:807-823.
38. Cash A.D., Aliev G., Siedlak S.L., et al. Microtubule reduction in Alzheimer's disease and aging is independent of tau filament formation. Am J Pathol 2003, 162:1623-1627.
39. Scarmeas N., Stern Y., Tang M.X., et al. Mediterranean diet and risk for Alzheimer's disease. Ann Neurol 2006, 59:912-921.
40. Bush A.I. Drug development based on the metals hypothesis of Alzheimer's disease. J Alzheimers Dis 2008, 15:223-240.
41. Jaya Prasanthi R.P., Schommer E., Thomasson S., et al. Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease. Mech Ageing Dev 2008, 129:649-655.
42. Castellani R.J., Lee H.G., Zhu X., et al. Neuropathology of Alzheimer disease: pathognomonic but not pathogenic. Acta Neuropathol 2006, 111:503-509.
43. Montine T.J., Phelps C.H., Beach T.G., et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 2012, 123:1-11.
44. Ferrer I. Defining Alzheimer as a common age-related neurodegenerative process not inevitably leading to dementia. Prog Neurobiol 2012, 97:38-51.