Abeta

S. Abeta and K. Imada, Kaisetsu Senyo Kagaku (Comprehensive Dyestuff Chemisty), Stukisensha, Osaka, 1989, p. 310. 

The enzymes that are involved in the processing of APP into amyloid peptides are known as secretases. Beta-secretase is an enzyme that catalyzes the initial proteolytic event leading to the production of Abeta amyloid peptides. If APP is cleaved by beta-secretase it can then be further cleaved by gamma-secretase. Abeta peptides are either secreted or intracellularly released. They have varying lengths and represent intermediate degradation products of its precursor (i.e., (3-secretase cleaved APP). Especially the 42 amino acid peptide (A 342) aggregates to form insoluble amyloid plaques. 

Garzon-Rodriguez W, Sepulveda-Becerra M, Milton S, Glabe CG. Soluble amyloid Abeta-(l-40) exists as a stable dimer at low concentrations. J Biol Chem 1997 272 21037-21044. 

Flarper JD, Wong SS, Lieber CM, Lansbury PT. Observation of metastable Abeta amyloid protofibrils by atomic force microscopy. Chem Biol 1997 4 119-125. 

Li L, Darden TA, Bartolotti L, Kominos D, Pederson LG. An atomic model for the pleated beta-sheet structure of Abeta amyloid protofilaments. Biophys J 1999 76 2871-2878. 

Roher AE, Chaney MO, Kuo YM, Webster SD, Stine WB, Haverkamp LJ, Woods AS, Cotter RJ, Tuohy JM, Krafft GA, Bonnell BS, Emmerling MR. Morphology and toxicity of Abeta-(l-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer s disease. J Biol Chem 1996 ... 

Wood SJ, MacKenzie L, Maleeff B, Hurle MR, Wetzel R. Selective inhibition of Abeta fibril formation. J Biol Chem 1996 271 4086-4092. 

Sikorski, P., Atkins, E. D., and Serpell, L. C. (2003). Structure and texture of fibrous crystals formed by Alzheimer s abeta(ll-25) peptide fragment. Structure (Comb.) 11, 915—926. 

Torok, M., Milton, S., Kayed, R., Wu, P., Mclntire, T., Glabe, C. G., and Langen, R. (2002). Structural and dynamic features of Alzheimer s Abeta peptide in amyloid fibrils studied by site-directed spin labeling. / Biol. Chem. 277, 40810-40815. 

For example, if then the stationary PDF will be Gaussian. On the other hand, abeta PDF will result... 

Bitan, G., Kirkitadze, M.D., Lomakin, A., Vollers, S.S., Benedek, G.B., and Teplow, D.B., Amyloid beta-protein (Abeta) assembly Abeta 40 and Abeta 42 oligomerize through distinct pathways, Proc. Natl. Acad. Sci. USA, 100, 330, 2003. 

LeVine, H., The challenge of inhibiting Abeta polymerization, Curr. Med. Chem., 9,1121, 2002. 

Oddo, S., Caccamo, A., Shepherd, J.D., Murphy, M.P., Golde, T.E., Kayed, R., Metherate, R., Mattson, M.P., Akbari, Y., and LaFerla, F.M., Triple-transgenic model of Alzheimer s disease with plaques and tangles intracellular Abeta and synaptic dysfunction, Neuron, 39, 409, 2003. 

DeMattos, R.B., Cirrito, J.R., Parsadanian, M., May, P.C., O Dell, M.A., Taylor, J.W., Harmony, J.A., Aronow, B.J., Bales, K.R., Paul, S.M., and Holtzman, D.M., ApoE and clusterin cooperatively suppress abeta levels and deposition evidence that ApoE regulates extracellular abeta metabolism in vivo, Neuron, 41,193, 2004. 

Fernandez-Vizarra, P., Fernandez, A.P., Castro Blanco, A. et al. (2004) Intra- and extracellular Abeta and PHF in clinically evaluated cases of Alzheimer s disease. Histol. HistopathoL, 19, 823-844. 

Ishii, K., Tokuda, T., Matsushima, T., etal. (2003) Pravastatin at lOmg/day does not decrease plasma levels of either amyloid-beta (Abeta)40 or Abeta42 in humans. Neurosci. Lett, 350, 161-164. 

Kuo, Y.M., Emmerling, M.R., Bisgaier, C.L., et al. (1998) Elevated low-density lipoprotein in Alzheimer s disease correlates with brain Abeta 1 2 levels. Biochem. Biophys. Res. Commun., 252, 711-715. 

Mann, D.M., Iwatsubo, T., Pickering-Brown, S.M., Owen, F., Saido, T.C., Perry, R.H. (1997) Preferential deposition of amyloid beta protein (Abeta) in the form of Abeta40 in Alzheimer s disease associated with a gene dosage effect of the apolipoprotein E E4 aUele. Neurosci. Lett., 221, 81-84. 

B7. Blasko, I., Wagner, M., Whitaker, N., Grubeck-Loebenstein, B., and Jansen-Durr, R, The amyloid beta peptide abeta (25-35) induces apoptosis independent of p53. FEES Lett. 470,221-225 (2000). 

Atwood CS, Moir RD, Huang X, Scarpa RC, Bacarra NM, Romano DM, Hartshorn MA, Tanzi RE, Bush AI. 1998. Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis. J Biol Chem 273 12817-12826. 

Bayer TA, Schafer S, Simons A, Kemmling A, Kamer T, Tepest R, Eckert A, Schussel K, Eikenberg O, Sturchler-Pierrat C, Abramowski D, Staufenbiel M, Multhaup G. 2003. Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Proc Natl Acad Sci USA 100 14187-14192. 

Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI. 1999b. Cu(II) potentiation of Alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 274 37111-37116. 

Lue L. F., Brachova L., Civin W. H., and Rogers J. (1996). Inflammation, Abeta deposition, and neurofibrillary tangle formation as correlates of Alzheimer s disease neurodegeneration. J. Neu-ropathol. Exp. Neurol. 55 1083-1088. 

Businaro R, Leone S, Fabrizi C, Sorci G, Donato R, Lauro GM, Fumagalli L. 2006. S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses. J Neurosci Res 83(5) 897-906. 

Billings, L. M., Oddo, S., Green, K. N., McGaugh, J. L., and LaFerla, F. M. (2005). Intraneuronal Abeta causes die onset of early Alzheimer s disease-related cognitive deficits in transgenic mice. Neuron... 

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