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Research Article

Editorial Central & Peripheral Nervous Systems: Amyloid β Peptide in Alzheimer's Disease Pathology: Towards a Rational Basis for Drug Discovery?

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Pages 263-270 | Published online: 03 Mar 2008

References

  • BLASS JP, BRODY EM, BUCKWALTER KC, CHAVKIN D,DAVIS KL, DRACHMAN DA, FRENCH DK, GWYTHER L, HITCHCOCK EA, JAZWIECKI TJ, KANE RL, KATZMAN R, LARSON EB, WEINSTEIN LH, WIENER JM: Report of the advisory panel on Alzheimer's disease. Department of Health and Human Services (DHHS) Publication No. (ADM) 89–1644. Washington, DC, US Government Printing Office (1989).
  • SELKOE DJ: Normal and abnormal biology of the betaamyloid precursor protein. Ann. Rev. Neurosci. (1994)17:489-517. An up to date review by one of the seminal figures in the Alzheimer's research community.
  • CHARTIER-HARLIN MC, CRAWFORD F, HOULDEN H, WAR-REN A, HUGHES D, FIDANI L, GOATE A, ROSSOR M, ROQUES P, HARDY J, MULLAN M: Early onset Alzheimer'OS disease caused by mutations at codon 717 of the P-amy-loid precursor protein gene. Nature (1991) 353:844–846.
  • TANZI R, ST GEORGE-HYSLOP P, GYSEELA JF: Molecular genetics of Alzheimer disease amyloid. J. Biol. Chem. (1991) 266:20579–20582.
  • GRAHAM DI, GENTLEMAN SM, LYNCH A, ROBERTS GW:
  • Distribution of P-amyloid protein in the brain following severe head injury. Neuropathol. Appl. Neurobiol. (1995) 21:27-34. An interesting paper that documents the appearance of A13 in children following the acute phase response of nerve cells to head trauma. Interestingly, Williams' syndrome, a genetic disorder asso-ciated with mental retardation has been shown in a thirty-five year old male to be associated with presenile plaque formation and neurofibrillary tangles (Golden et al.: Arch. Neurol. (1995) 52:209–212).
  • COYLE JT, PRICE DL, DELONG MR: Alzheimer's disease: a disorder of cortical cholinergic innervation. Science (1983) 219:1184–1190.
  • KOSIK K: Alzheimer plaques and tangles: advances on both fronts. Trends Pharmacol. Sci. (1991) 14:218-219. A very interesting and accessible overview on the current status of tau protein phosphorylation in AD.
  • SISODIA S, KOO E, BAYREUTHER K, UNTERBECK A, PRICE D: Evidence that 3-amyloid protein in Alzheimer's dis-ease is not derived by normal processing. Science (1990) 248:492–495.
  • NASLUND J, SCHIERHORN A, HELLMAN U, LANNFELT L,ROSES AD, TJERNBERG LO, SILBERRING J, GANDAY SE, WINBLAD B, GREENGARD P, NORDSTEDT C, TERNEIUS L: Relative abundance of Alzheimer Al amyloid peptide variants in Alzhehner disease and normal aging. Proc. Natl. Acad. Sci. USA (1994) 91:8378–8382.
  • ALLSOP D, CLEMENTS A, KENNEDY H, WALSH D, WIL-LIAMS C: Mechanism of cerebral amyloidosis in Alzhe-imer's disease. In: Amyloid Protein Precursor in Development, Aging and Alzheimer's Disease. CL Masters et al. (Eds.). Springer Verlag, Berlin (1994):46–59.
  • KNOPS J, SUOMENSAARI S, LEE M, MCCONOLOGUE L, SUEBERT P, SINHA S: Cell-type and amyloid precursor protein-type specific inhibition of AP release by bafilomycin Al, a selective inhibitor of vacuolar ATP-ases. J. Biol. Chem. (1995) 270:2419-2422. A paper from the Athena group reporting on the effects of a first generation P-secretase inhibitor on Al release.
  • YANKNER BA, DAWES LR, FISHER S, VILLA-KOMAROFF L,OSTER-GRANITE ML, NEVE RL: Neurotoxicity of a frag-ment of the amyloid precursor associated with Alzhe-imer's disease. Science (1989) 245:417–420.
  • CITRON M, OLTERSDORF T, HAASS C, MCCONOLOGUE L,HUNG AY, SEUBERT P, VIGO- PELFREY C, LIBERBERG I, SELKOE DJ: Mutation of the 3-amyloid precursor protein in familial Alzheimer's disease increases 13-protein pro-duction. Nature (1992) 360:672–674.
  • CAI X-D, GOLDE DE, YOUNKIN SG. Release of excess amyloid p protein from a mutant amyloid 3 protein precursor. Science (1993) 259:514–516.
  • HARDY J, HIGGINS G: Alzheimer's disease: the amyloid cascade hypothesis. Science (1992) 256:184–185.
  • 'WHITSON JS, SELKOE DJ, COTMAN CW: Amyloid p pro-tein enhances the survival of hippocampal neurons in vitro. Science (1989) 243:1488–1490.
  • NVIRAK D, BAYNEY R, RAMABHADARAN TV, FRACASSORP, HART JT, HAUER PE, HSIAU P, PEKAR SK, SCANGOS GA, TRAPP BD, UNTERBECK AJ: Deposits of amyloid P protein in the central nervous system of transgenic mice. Science (1991) 253:323–325.
  • QUON, D, CATALANO WR, SCARDINA JM, MURAKAMI K,CORDELL B: Fonnation of beta-amyloid protein deposits in brains of transgenic mice. Nature (1991) 352:239–241.
  • KAWABATA S, HIGGINS GA, GORDON JW: Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing a C-terminal fragment of human amyloid precursor protein. Nature (1991) 354:476–478.
  • MARX J: Major setback for Alzheimer's models. Science (1992) 255:1200-1202. The background to the failed transgenic models.
  • KRAFFT G: Perspectives on amyloid and Alzheimer's disease: a critical review. Ann. Rep. Med. Chem. (1993) 28:49-58. A good, although inevitably dated, overview of the amyloid hypothe-sis of AD. It is especially valuable in that it takes a critical, as opposed to a descriptive, perspective.
  • CUTLER NR, SRAMEK JJ, VEROFF AE: Alzheimer's Disease.
  • ?Optimizing Drug Development Strategies. Wiley, Chichester, UK (1994):38–39, An outstanding book covering all aspects of current approaches to AD drug development. In addition to discussing current discovery approaches, the authors discuss clinical assessment techniques for the evaluation of Al) patients. Of especial note is Chapter 9, "Finding the dose: the bridging study" that provides the rationale for the use of patients in Phase I CNS trials. Required reading for those designing and those funding Alzheimer trials.
  • LAFERLA FM, TINKLE BL, BlEBERICH CJ, HAUDENSCHILD ?CC, JAY G: The Alzheimer's Al peptide induces neurode-generation and apoptotic cell death in transgenic mice. Nature Genetics (1995) 9:21-30. A very interesting, if ultimately limited, effort in the area of trans-genies. The lack of information on Al expression in the N-CAM constructs is disappointing.
  • GAMES D, ADAMS D, ALESSANDRINI R, BARBOUR R, esBERTHELEI IL P, BLACKWELL C, CARR T. CELMENS J,DONALDSON T, GILLESPIE F, GUIDO T, HAGPLAN S, JOHNSON- WOOD K, KHAN K, LEE M, LIEBOWITZ P, LIEBERBERG I, LITTLE S, MASLIAH E, MCCONOLOGUE L, MONTOYA-ZAVALA M, MUCKE L, PAGANINI L, PENNIMAN E: Alzheimer-type neuropathology in transgenic mice overexpressing V717F P-amyloid precursor protein. Nature (1995) 373:523–527.
  • A paper that has created considerable interest with a full half page of comment - "...a rare piece of good news from the beleaguered biotechnology industry" - in an article entitled "Athena Neurosciences makes itself heard in battle against Alzheimer's" by Lawrence M Fisher in the New York Times Business Section on February 15th, 1995. A major milestone in the AD research area that was praised by investigators outside Athena for the willingness of Ivan Liberberg to share his slides before publication. However, at the recent IBC Conference on AD in London (see [511), there were some comments from other companies in that the strain of mouse used for the transgenic studies was not mentioned and no tangles were found. The former appears to be due to space constraints at Nature since Athena have made this information available on the Internet. The latter comments may reflect the temporal sequence of the pathology, with plaques appearing before tangles. Interestingly, se nalagmca. tem,-8.ROUSH W: Protein studies try to puzzle out Alzheimer's ..tangles. Science Athena did not develop this model but bought the company that did, Exemplar, for $3 million when the latter encountered financial difficulties. There but for the grace of Godcould have goneother enterprising pharmaceutical companies!
  • YANKNER BA, DUGGY LK, KIRSCHNER DA: Neurotrophic and neurotoxic effects of amyloidp protein: reversal by tachykinin neuropeptides. Science (1990) 250:279–282.
  • KOWALL NW, BEAL MF, BUSCIGLIO JE, DUFFY LK, YANK-NER BA An in vivo model for the neurodegenerative effects of 13-amyloid and protection by substance P. Proc. Natl. Acad. Sci. USA (1991) 88:7247–7251.
  • MAY PC, GI Fl ER BD, WATERS DC, SIMMONS LK, BECKERGW, SMALL JS, ROBISON PM: 13-Amyloid peptide in vitro toxicity: lot-to-lot variability. Neurobiol. Aging. (1992) 13:605-607. Based on the last Society for Neuroscience Meeting, not too many people are familiar with this paper which documents differences in six lots of chemically identical AP 1–40.
  • PIKE CJ, WALENCEWICZ AJ, GLABE CG, COTMAN CW: Aggregation-related toxicity of synthetic13-amylokl pro-tein in hippocampal cultures. Eur. J. Pharrnacol. (1991) 207:367–368.
  • SOTO C, BRANES MC, ALVAREZ J, INESTROSA NC: Struc-tural determinants of the Alzheimer's amyloid 13-pep-tide. J. Neurocheni. (1994) 63:1191–1198.
  • PIKE CJ, BURDICK D, WALENCEWICZ AJ, GLABE CG, COTMAN CW: Neurodegeneration induced by [3-amyloid peptides in vivo; the role of peptide assembly state. J. Neurosci. (1993) 13:1676–1687.
  • BRANDAN E, INESTROSA N: Extracellular matrix compo-nents and amyloid in neuritic plaques of Alzheimer's disease. Gen. Pharmacol. (1993) 24:1063–1068.
  • MA J, YEE A, BREWER JR FIB, DAS S, P01 IER H: Amyloid-associated proteins a 1-antichymotrypsin and apolipo-protein E promote assembly of Alzheimer 13-protein Into filaments. Nature (1994) 372:92-94. A very interesting paper that generated considerable interest given the potential role of ApoE in AD pathology. While the two chaperones were shown to influence AP filament formation, no studies were done to ascertain whether the resultant AP products were neurotoxic.
  • STRITTMATER WJ, SAUNDERS AM, SCHMECHEL D, PERI-CAK-VANCE M, ENGHILD J, SALVESEN GS, ROSES AD: Apolipoprotein E: high avidity binding to 13-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA (1993) 90:1977–1981.
  • NATHAN BP, BELLOSTA S, SANAN DA, WEISGRABER KH,MAHLEY RW, PITAS RE: Differential effects of apolipo-proteins E3 and E4 on neuronal growth in vitro. Science (1994) 264:850–852.
  • LADU MJ, FALDUTO MT, MANIELLI AM, REARDON CA,GETZ GS, FRAIL DE: Isoform-specific binding of apolipo-protein E to 13-amyloid. J. Biol. Chem. (1994) 269:23403–23406.
  • LEHMANN J: Novel Al) hypotheses. Drug News Persp •(1995) 8:60-64. A meeting report from the IBC Conference held in Philadelphia in September of 1994. In addition to May's work on amylin-induced neurotoxicity and the Gliatech observation that AP deposits are non toxic, highlights included Peter Davies' critique of the amyloid hypothesis of AD, transgenic APP models from GenPharm and the University of Minnesota and Leon Thal's efforts on the Alzheimer's Disease Cooperative Study Unit (ADCSU), a clinical trial program for potential AD drugs funded by the NIA.
  • KOWLOWSKI MR, SAPNOYANNIS A, MANLY SP, FIDEL SA,NEVE RE: The neurotoxic carboxy-terminal fragment of the Alzheimer amyloid precursor protein binds specifi-cally to a neuronal cell surface molecule: pH depend-ence of the neurotoxicity and the binding. J. Neurosci. (1992) 12:1679–1687.
  • MCGEER PL, ROGERS J: Anti-inflammatory agents as atherapeutic approach to Alzheimer's Disease. Neurol. (1992) 44:447–449.
  • ROGERS J COOPER NR, WEBSTER S, SCHULTZ J, MCGEERPL, STYREN SD, CIVIN WH, BRACHOVA L, BRADT B, WARD P, LIEBERBERG I: Complement activation by 3-amyloid In Alzheimer disease. Proc. Natl. Acad. Sci. USA (1992) 89:10016–10020.
  • JIANG H, BURDICK D, GLABE CG, COTMAN CW, TENNER AJ: 13-Amyloid activates complement by binding to a specific region of the collagen-like domain of the Clq A chain. J. Immunol. (1994) 152:5050–5059.
  • EIKELENBOOM P, ZHAN S-S, VAN GOOL WA, ALLSOP D: Inflammatory mechanisms in Alzheimer's disease. Trends Pharmacol. Sci. (1994) 15:447-450. An excellent overview of the role of complement and cytokines in AD.
  • FORLONI G, CHIESA R, SMIROLDO S, VERGAL, SALMONA M, TAGLIAVINI F, ANGERETTI N: Apoptosis mediated neurotoxicity induced by chronic application of f3 amy-loid fragment 25-35. NeuroReport (1993) 4:523–526.
  • LOO DT, COPAN' A, PIKE CJ, WHIITEMORE ER, WALEN-CIEWICZ AJ, COTMAN CW: Apoptosis is induced by 13-amyloid in cultured central nervous system neurons. Proc. Natl. Acad. Sci. USA (1993) 90:7951–7955.
  • THOMPSON CB: Apoptosis in the pathogenesis and treatment of disease. Science (1995) 267:1456–1462.
  • SHEARMAN MS, RAGAN CI, IVERSEN LL: Inhibition of
  • PC12 cell redox activity is a specific, early indicator ofthe mechanism of 13-amyloid-mediated cell death. Proc. Natl, Acad. Sci. USA (1994) 91:1470-1474. An interesting paper highlighting the role of oxidative stress in neuronal death. The possible role of an AP receptor akin to that proposed for prion proteins is discussed in this paper, on page 1472. If this postulated receptor is anywhere near the complexity of the prion recognition site proposed by Pruisner, it is hardly surprising that the interactions of AP in the CNS and in vitro appear so complex.
  • BEHL C, DAVIS J, COLE GM, SCHUBERT D: Vitamin E protects nerve cells from amyloid 13 protein toxicity. Biochem. Biophys. Res. Comm. (1992) 186:944–952.
  • BEHL C, HOVELY L, KRAJEWSKI S, SCHUBERT D, REED JC: Bc1-2 prevents killing of neuronal cells by glutamate but not by amyloid beta protein. Biochem. Biophys. Res. Comm. (1993) 197:949–956.
  • BEHL C, DAVIS JB, KLIER FG, SCHUBERT D: Amyloid peptide induces necrosis rather than apoptosis. Brain Res. (1994) 645:253–264.
  • LAMB BT: Malting models for Alzheimer's disease. Na-ture Genetics (1995) 9:4–6.
  • IBC MEETING: Alzheimer's Disease: Molecular Aspects.March 6th and 7th, 1995, Cavendish Conference Centre, London. IBC appears to be sponsoring these meetings at the rate of one every six months which is, hopefully, an indication of the progress being made in the area. Highlights from this meeting included the elegant and extensive research efforts of the SmithKline Beecham Molecular Neuropathology Group, Cordell's mention of a specific inhibitor of C-terminal amyloid peptide formation from MMD (to be published in the March issue of Neuron) and a 13-APP751 transgenic from Scios-Nova that showed both plaque and tangle formation and behavioural impairment with age but has yet to be subject to peer review.
  • YAMAGUCHI F, RICHARDS SJ, BEYREUTHER K, SALBAUM M, CARLSON GA, DUNNETT SA: Transgenic mice for the amyloid precursor protein 695 isofonn have impaired spatial memory. NeuroReport (1991) 2:781–784.
  • NITSCH RM, GROWDONSH, FARBER SA, DENG M, WURT-MAN RJ: Regulation of APP processing by first messen-gers. In: Alzheimer's Disease: Therapeutic Strategies. E Giacobini, R Becker (Eds.). Birkhauser, Boston (1994):54–61.
  • GREENBERG BD, MURPHY MF: Toward an integrated discovery and development program in Alzhehner's disease: the amyloid hypothesis. Neurobiot Aging (1994) 15\(Suppl. 2):S105-S109. An overview of the complexities and pragmatic choices associated with any type of drug discovery program in the Alzheimer's disease area
  • WILLIAMS M: The decade of the brain initiative and..health care reform: irreconcilable differences? Exp.Opin. Invest. Drugs (1994) 3:947-954. An overview of current activities in CNS research in the pharmaceu-tical industry with a consideration of the complexity and expense of clinical trials. Michael Williams, Kazumi Shiosaki & Pamela Puttfarcken, Neurosci-ence Discovery, Pharmaceutical Products Division, Abbott Labora-tories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.

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