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Intended pharmacotherapeutical approaches of Alzheimer’s disease therapy


Authors: Jan Korábečný1 ,2;  Eva Hrubá 3;  Ondřej Soukup 2;  Filip Zemek 2;  Kamil Musílek 4;  Eugenie Nepovímová 1;  Katarína Špilovská 2;  Veronika Opletalová 1;  Kamil Kuča 5
Authors place of work: Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, Katedra farmaceutické chemie a kontroly léčiv 1;  Univerzita obrany, Fakulta vojenského zdravotnictví, Katedra toxikologie, Hradec Králové 2;  Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, katedra farmakologie a toxikologie 3;  Univerzita Hradec Králové, Přírodovědecká fakulta, Katedra chemie 4;  Univerzita obrany, Fakulta vojenského zdravotnictví, Centrum pokročilých studií a Fakultní nemocnice Hradec Králové 5
Published in the journal: Čes. slov. Farm., 2012; 61, 4-10
Category: Review Articles

Summary

Alzheimer’s disease is a progressive neurodegenerative disorder mainly manifested by memory loss, personality changes, and cognitive dysfunction. Despite the fact that tireless research is being conducted, up-to-date pharmacotherapy of AD is presented only by two groups diverging in the mechanism of action. The larger one uses acetylcholinesterase inhibitors, and the second group is represented by the N-methyl-D-aspartate antagonist memantine. Even though the etiology of Alzheimer’s disease is unknown, several different therapeutic approaches are being investigated. The aim of this paper is to provide an overview of the present state of intended therapeutics for AD, describing their mechanism of action if known, displaying chemical structures, and the state of clinical trials if any.

Keywords:
Alzheimer’s disease • acetylcholinesterase • therapeutic approaches • beta amyloid • tau protein


Zdroje

1.  Alzheimer’s Association. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 2011; 7, 208–244.

2. Herrup K. Re imaginizing Alzheimer’ disease – an age-based hypothesis. J Neurosci 2010; 30, 16755–16762

3. Drtinova L., Pohanka M. Alzheimerova demence: aspekty současné farmakologické léčby. Čes slov Farm 2011; 60, 219–228.

4. Craig D., Mirakhur A., Hart D. J., McIlroy S. P., Passmore A. P. A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer’s disease. Am J Geriat Psychiat 2005; 13, 460–468.

5. Ballard C., Gauthier S., Corbett A., Brayne C., Aarsland D., Jones E. Alzheimer’s disease. Lancet 2011; 377, 1019–1031.

6. Brodaty H., Breteler M. M., Dekosky S. T., Dorenlot P., Fratiglioni L., Hock C., Kenigsberg P. A., Scheltens P., De Strooper B. The world of dementia beyond 2020. J Am Geriatr Soc 2011; 59, 923–927.

7. Souder E., Beck C. Overview of Alzheimer’s disease. Nurs Clin N Am 2004; 39, 545–559.

8. Kim K. Y., Wood B. E., Wilson M. I. Risk factors for Alzheimer’s disease: An overview for clinical practitioners. Consult Pharm 2005; 20, 224–230.

9. Bateman R. J., Aisen P. S., De Strooper B., Fox N. C., Lemere C. A., Ringman J. M., Salloway S., Sperling R. A., Windisch M., Xiong C. Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimers Res Ther 2011; 3, 1–13.

10. Giacobini E. Do cholinesterase inhibitors have disease-modifying effects in Alzheimer’s disease? CNS Drugs 2001; 15, 85–91.

11. Giacobini E., Mori F., Lai C. C. The effect of cholinesterase inhibitors on the secretion of APPS from rat brain cortex. Ann NY Acad Sci. 1996; 777, 393–398.

12. Knapp M. J., Knopman D. S., Solomon P. R., Pendlebury W. W., Davis C. S., Gracon S. I. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. JAMA 1994; 271, 985–991.

13. Dejmek L. 7-Meota. Drug Future 1990; 15, 126–129.

14. Korabecny J., Musilek K., Holas O., Binder J., Zemek F., Marek J., Pohanka M., Opletalova V., Dohnal V., Kuca K. Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinestrase inhibitors in Alzhemeir disease. Bioorg Med Chem Lett 2010; 20, 6093–6095.

15. Korabecny J., Holas O., Musilek K., Pohanka M., Opletalova V., Dohnal V., Kuca K. Synthesis and in vitro evaluation of new tacrine derivatives-bis-alkylene linked 7-MEOTA. Lett Org Chem 2010; 7, 327–331.

16. Korabecny J., Musilek K., Holas O., Nepovimova E., Jun D., Zemek F., Opletalova V., Patocka J., Dohnal V., Nachon F., Hroudova J., Fisar Z., Kuca K. Synthesis and in vitro evaluation of N-(bromobut-3-en-2-yl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer’s disease treatment. Molecules 2010; 15, 8804–8812.

17. Korabecny J., Musilek K., Zemek F., Horova A., Holas O., Nepovimova E., Opletalova V., Hroudova J., Fisar Z., Jung Y.-S., Kuca K. Synthesis and in vitro evaluation of 7-methoxy-N-(pent-4-enyl)-1,2,3,4-tetrahydroacridin-9-amine – new tacrine derivative with cholinergic properties. Bioorg Med Chem Lett 2011; 21, 6563–6556.

18. Fang L, Appenroth D., Decker M., Kiehntopf M., Lupp A., Peng S., Fleck C., Zhang Y., Lehman J. NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity. J Med Chem 2008; 51, 7666–7669.

19. Trinh, N. H., Hoblyn, J., Mohanty, S., Yaffe, K. Efficacy of cholinesterases inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA 2003; 289, 210–216.

20. Kamal, M. A., Klein, P., Yu, Q. S., Tweedie, D., Li, Y., Holloway, H. W., Tweedie, D., Greig, N. H. Kinetics of human serum butyrylcholinesterase and its inhibition by a novel experimental Alzheimer therapeutic, bisnorcymserine. J Alzheimers Dis 2006; 10, 43–51.

21. Li F., Tsien J. Z. Memory and the NMDA receptors. New Engl J Med 2009; 361, 302–303.

22. Harkany T., Abraham I., Timmerman W., Laskay G., Toth B., Safari M., Konya C., Sebens J. B., Korf J., Nyakas C., Zarandi M., Soos K., Penke B., Luiten P. G. Beta-amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis. Eur J Neurosci 2000; 12, 2735–2745.

23. Amadoro G., Ciotti M. T., Costanzi M., Cestari V., Calissano P., Canu N. NMDA receptor mediates tau–induced neurotoxicity by calpain and ERK/MAPK activation. P Natl Acad Sci USA 2006; 103, 2892–2897.

24. Sonkusare S. K., Kaul C. L., Ramarao P. Dementia of Alzheimer’s disease and other neurodegenerative disorders-memantine, a new hope. Pharmacol Res 2005; 51, 1–17.

25. Tariot P. N., Farlow M. R., Grossberg G. T., Graham S. M., McDonald S., Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004; 291, 317–324.

26. Wenk G. L., Baker L. M., Stoehr J. D., Hauss-Wegrzyniak B., Danysz W. Neuroprotection by novel antagonists at the NMDA receptor channel and glycineB sites. Eur J Pharmacol. 1998; 347, 183–187.

27. Schenk D., Barbour R., Dunn W., Gordon G., Grajeda H., Guido T., Hu K., Huang J., Johnson-Wood K., Khan K., Kholodenko D., Lee M., Liao Z., Lieberburg I., Motter R., Mutter L., Soriano F., Shopp G., Vasquez N., Vandevert C., Walker S., Wogulis M., Yednock T., Games D., Seubert P. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999; 400, 173–177.

28. Lavie V., Becker M., Cohen-Kupiec R., Yacoby I., Koppel R., Wedenig M., Hutter-Paier B., Solomon B. EFRH-phage immunization of Alzheimer’s disease animal model improves behavioral performance in Morris water maze trials. J Mol Neurosci 2004; 24, 105–113.

29. Orgogozo J. M., Gilman S., Dartigues J. F., Laurent B., Puel M., Kirby L. C., Jouanny P., Dubois B., Eisner L., Flitman S., Michel B. F., Boada M., Frank A., Hock C. Subacute meningoencephalitis in a subset of patients with AD after A beta 42 immunization. Neurology 2003; 61, 46–54.

30. Hock C., Konietzko U., Streffer J. R., Tracy J., Signorell A., Müller-Tillmanns B., Lemke U., Henke K., Moritz E., Garcia E., Wollmer M. A., Umbricht D., de Quervain D. J., Hofmann M., Maddalena A., Papassotiropoulos A., Nitsch R. M. Antibodies against beta-amyloid slow cognitive decline in Alzheimer’s disease. Neuron 2003; 38, 547–554.

31. Fox N. C., Black R. S., Gilman S., Rossor M. N., Griffith S. G., Jenkins L., Koller M. Effects of A beta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 2005; 64, 1563–1572.

32. Dodel R. C., Du Y., Depboylu C., Hampel H., Frölich L., Haag A., Hemmeter U., Paulsen S., Teipel S. J., Brettschneider S., Spottke A., Nölker C., Möller H. J., Wei X., Farlow M., Sommer N., Oertel W. H. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosur Ps 2004; 75, 1472–1474.

33. Asai M., Hattori C., Iwata N., Saido T. C., Sasagawa N., Szabó B., Hashimoto Y., Maruyama K., Tanuma S., Kiso Y., Ishiura S. The novel beta-secretase inhibitor KMI-429 reduces amyloid beta peptide production in amyloid precursor protein transgenic and wild-type mice. J Neurochem 2006; 96, 533–540.

34. Wong P. BACE. Alzheimers Dement 2005; 1, S3.

35. Citron M. Beta-secretase inhibition for the treatment of Alzheimer’s disease-promise and challenge. Trends Pharmacol Sci 2004; 25, 92–97.

36. Mancini F., de Simone A., Andrisano V. Beta-secretase as a target for Alzheimer’s disease drug discovery: an overview of in vitro methods for characterization of inhibitors. Anal Bioanal Chem 2011; 400, 1979–1996.

37. Lanz T. A., Himes C. S., Pallante G., Adams L., Yamazaki S., Amore B., Merchant K. M. The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester reduces A beta levels in vivo in plazma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice. J Pharmacol Exp Ther 2003; 305, 864–871.

38. El Mouedden M., Vandermeeren M., Meert T., Mercken M. Reduction of A beta levels in the Sprague Dawley rat after oral administrativ of the functional gamma-secretase inhibitor, DAPT: a novel non-transgenic model for A beta production inhibitors. Curr Pharm Design 2006; 12, 671–676.

39. May P. C., Yang Z., Li W., Hyslop P. A., Siemers E., Boggs L. N. Multi-compartmental pharmacodynamic assessment of the functional gamma-secretase inhibitor LY450139 dihydrate in PDAPP transgenic mice and non-transgenic mice. Neurobiol Aging 2004; 25, S65.

40. Barten D. M., Guss V. L., Cosa J. A., Loo A., Hansel S. B., Zheng M., Munoz B., Srinivasan K., Wang B., Robertson B. J., Polson C. T., Wang J., Roberts S. B., Hendrick J. P., Anderson J. J., Loy J. K., Denton R., Verdoorn T. A., Smith D. W., Felsenstein K. M. Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor. J Pharmacol Exp Ther 2005; 312, 635–643.

41. Imbimbo B. P. Alzheimer’s disease: gamma secretase inhibitors. Drug Discov Today: Therapeutic Strategies 2008; 5, 169–175.

42. Weggen S., Eriksen J. L., Sagi S. A., Pietrzik C. U., Golde T. E., Koo E. H. A beta 42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain. J Biol Chem 2003; 278, 30748–30754.

43. Becker R. E., Greig N. H. Why so few drugs for Alzheimer’s disease? Are methods failing drugs? Curr Alzheimer Res 2010; 7, 642–651.

44. Mintzer J. E., Wilcock G. K., Black S. E., Zavitz K. H., Hendrix S. B. MPC-7869, a selective Abeta42-lowering agent, delays time to clinically significant psychiatric adverse events in Alzheimer’s disease: analysis from a 12-month phase 2 trial. Presented as a poster exhibit at the 10th International Conference on Alzheimer’s Disease and Related Disorders; 2006 Jul 15–20; Madrid, Spain.

45. Aisen P. S., Gauthier S., Vellas B., Briand R., Saumier D., Laurin J., Garceau D. Alzhemed: A potential treatment for Alzheimer’s disease. Curr Alzheimer Res 2007; 4, 473–478.

46. Bilikiewicz A., Gaus W. Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer’s disease. J Alzheimer Dis 2004; 6, 17–26.

47. Leszek J., Inglot A. D., Janusz M., Byczkiewicz F., Kiejna A., Georgiades J., Lisowski J. Colostrinin proline-rich polypeptide complex from ovine colostrum-a long-term study of its efficacy in Alzheimer’s disease. Med Sci Monitor 2002; 8, PI93–PI96.

48. Townsend M., Cleary J. P., Mehta T., Hofmeister J., Lesne S., O’Hare E., Walsh D. M., Selkoe D. J. Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers. Ann Neurol 2006; 60, 668–676.

49. Fassbender K., Simons M., Bergmann C., Stroick M., Lutjohann D., Keller P., Runz H., Kuhl S., Bertsch T., von Bergmann K., Hennerici M., Beyreuther K., Hartmann T. Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides A beta 42 and A beta 40 in vitro and in vivo. P Natl Acad Sci USA 2001; 98, 5856–5861.

50. Wolozin B., Kellman W., Ruosseau P., Celesia G. G., Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000; 57, 1439–1443.

51. Li G., Higdon R., Kukull W. A., Peskind E., Moore K. V., Tsuang D., van Belle G., McCormick W., Bowen J. D., Teri L., Schellenberg G. D., Larson E. B. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology 2004; 63, 1624–1628.

52. Jick H., Zornberg G. L., Jick S. S., Seshadri S., Drachman D. A. Statins and the risk of dementia. Lancet 2000; 356, 1627–1631.

53. Rockwood K., Kirkland S., Hogan D. B., MacKnight C., Merry H., Verreault R., Wolfson C., McDowell I. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002; 59, 223–227.

54. McGuiness B., O`Hare J., Craig D., Bullock R., Malouf R., Passmore P. Statins for the treatment of dementia (Review). Cochrane Database Syst Rev 2010; 4.

55. Yaffe K., Barrett-Connor E., Lin F., Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol 2002; 59, 378–384.

56. Rea T. D., Breitner J. C., Psaty B. M., Fitzpatrick A. L., Lopez O. L., Newman A. B., Hazzard W. R., Zandi P. P., Burke G. L., Lyketsos C. G., Bernick C., Kuller L. H. Statin use and the risk of incident dementia: the cardiovascular health study. Arch Neurol 2005; 62, 1047–1051.

57. Shepherd J., Blauw G. J., Murphy M. B., Bollen E. L., Buckley B. M., Cobbe S. M., Ford I., Gaw A., Hyland M., Jukema J. W., Kamper A. M., Macfarlane P. W., Meinders A. E., Norrie J., Packard C. J., Perry I. J., Stott D. J., Sweeney B. J., Twomey C., Westendorp R. G.; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360, 1623–1630.

58. Zandi P. P., Sparks D. L., Khachaturian A. S., Tschanz J., Norton M., Steinberg M., Welsh-Bohmer K. A., Breitner J. C.; Cache County Study investigators. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry 2005; 62, 217–224.

59. Wang Q., Yan J., Chen X., Li J., Yang Y., Weng J., Deng C., Yenari M. A. Statins: multiple neuroprotective mechanisms in neurodegenerative diseases. Exp Neurol 2011; 230, 27–34.

60. Craft S. Insulin resistance syndrome and Alzheimer’s disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging 2005; 26, S65–S69.

61. Pedersen W. A., McMillan P. J., Kulstad J. J., Leverenz J. B., Craft S., Haynatzki G. R. Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol 2006; 199, 265–273.

62. Watson G. S., Cholerton B. A., Reger M. A., Baker L. D., Plymate S. R., Asthana S., Fishel M. A., Kulstad J. J., Green P. S., Cook D. G., Kahn S. E., Keeling M. L., Craft S. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriat Psychiat 2005; 13, 950–958.

63. Geldmacher D. S., Frolich L., Doody R. S., Erkinjuntti T., Vellas B., Jones R. W., Banerjee S., Lin P., Sano M. Realistic expectations for treatment success in Alzheimer’s disease. J Nutr Health Aging 2006; 10, 417–429.

64. Craft S. Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications. Alz Dis Assoc Dis 2006; 20, 298 –301.

65. Gupta A., Bisht B., Dey C. S. Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes. Neuropharmacology 2011; 60, 910–920.

66. Cuajungco M. P., Frederickson C. J., Bush A. I. Amyloid-beta metal interaction and metal chelation. Sub-Cell Biochem 2005; 38, 235–254.

67. Cherny R. A., Atwood C. S., Xilinas M. E., Gray D. N., Jones W. D., McLean C. A., Barnham K. J., Volitakis I., Fraser F. W., Kim Y., Huang X., Goldstein L. E., Moir R. D., Lim J. T., Beyreuther K., Zheng H., Tanzi R. E., Masters C. L., Bush A. I. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 2001; 30, 665–676.

68. Ritchie C. W., Bush A. I., Mackinnon A., Macfarlane S., Mastwyk M., MacGregor L., Kiers L., Cherny R., Li Q. X., Tammer A., Carrington D., Mavros C., Volitakis I., Xilinas M., Ames D., Davis S., Beyreuther K., Tanzi R. E., Masters C. L. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol 2003; 60, 1685–1691.

69. Dedeoglu A., Cormier K., Payton S., Tseitlin K. A., Kremsky J. N., Lai L., Li X., Moir R. D., Tanzi R. E., Bush A. I., Kowall N. W., Rogers J. T., Huang X. Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer’s amyloidogenesis. Exp Gerontol 2004; 39, 1641–1649.

70. Lee J. Y., Friedman J. E., Angel I., Kozak A., Koh J. Y. The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol Aging 2004; 25, 1315–1321.

71. Reznichenko L., Amit T., Zheng H., Avramovich-Tirosh Y., Youdim M. B., Weinreb O., Mandel, S. Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer’s disease. J Neurochem 2006; 97, 527–536.

72. Fisher A., Pittel Z., Haring R., Bar-Ner N., Kliger-Spatz M., Natan N., Egozi I., Sonego H., Marcovitch I., Brandeis R. M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer’s disease: implications in future therapy. J Mol Neurosci 2003; 20, 349–356.

73. Fisher A., Brandeis R., Bar-Ner R. H., Kliger-Spatz M., Natan N., Sonego H., Marcovitch I., Pittel Z. AF150(S) and AF267B: M1 muscarinic agonists as innovative therapies for Alzheimer’s disease. J Mol Neurosci 2002; 19, 145–153.

74. Caccamo A., Fisher A., Laferla F. M. M1 Agonists as a potential disease-modifying therapy for Alzheimer’s disease. Curr Alzheimer Res 2009; 6, 112–117.

75. Caccamo A., Oddo S., Billings L. M., Green K. N., Martinez-Coria H., Fisher A., LaFerla F. M. M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 2006; 49, 671–682.

76. Hock C., Maddalena A., Raschig A., Müller-Spahn F., Eschweiler G., Hager K., Heuser I., Hampel H., Müller-Thomsen T., Oertel W., Wienrich M., Signorell A., Gonzalez-Agosti C., Nitsch R. M. Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of A beta (42) in patients with Alzheimer’s disease. Amyloid 2003; 10, 1–6.

77. Bodick N. C., Offen W. W., Levey A. I., Cutler N. R., Gauthier S. G., Satlin A., Shannon H. E., Tollefson G. D., Rasmussen K., Bymaster F. P., Hurley D. J., Potter W. Z., Paul S. M. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol 1997; 54, 465–473.

78. Fang L., Jumpertz S., Zhang Y., Appenroth D., Fleck C., Mohr K., Tränkle C., Decker M. Hybrid molecules from xanomeline and tacrine: enhanced tacrine actions on cholinesterases and muscarinic M1 receptors. J Med Chem 2010; 53, 2094–2103.

79. Mulugeta E., Karlsson E., Islam A., Kalaria R., Mangat H., Winblad B., Adem A. Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients. Brain Res 2003; 960, 259–262.

80. Heinrich JN, Butera JA, Carrick T, Kramer A, Kowal D, Lock T, Marquis KL, Pausch MH, Popiolek M, Sun SC, Tseng E, Uveges AJ, Mayer SC. Pharmacological comparison of muscarinic ligands: historical versus more recent muscarinic M1-preferring receptor agonists. Eur J Pharmacol 2009; 605, 53–56.

81. Neeper M., Schmidt A. M., Brett J., Yan S. D., Wang F., Pan Y. C., Elliston K., Stern D., Shaw A. Cloning and expression of a cell-surface receptor for advanced glycosylation end-products of proteins. J Biol Chem 1992; 267, 14998–15004.

82. Mackic J. B., Stins M., McComb J. G., Calero M., Ghiso J., Kim K. S., Yan S. D., Stern D., Schmidt A. M., Frangione B., Zlokovic B. V. Human blood-brain barrier receptors for Alzheimer’s amyloid-h 1–40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer. J Clin Invest 1998; 102, 734–743.

83. Deane R., Du Yan S., Submamaryan R. K., LaRue B., Jovanovic S., Hogg E., Welch D., Manness L., Lin C., Yu J., Zhu H., Ghiso J., Frangione B., Stern A., Schmidt A. M., Armstrong D. L., Arnold B., Liliensiek B., Nawroth P., Hofman F., Kindy M., Stern D., Zlokovic B. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9, 907–913.

84. Matsuoka Y., Saito M., LaFrancois J., Saito M., Gaynor K., Olm V., Wang L., Casey E., Lu Y., Shiratori C., Lemere C., Duff K. Novel therapeutic approach for the treatment of Alzheimer’s disease by peripheral administration of agents with an affinity to betaamyloid. J Neurosci 2003; 23, 29–33.

85. Bachmeier C., Beaulieu-Abdelahad D., Mullan M., Paris D. Selective dihydropyiridine compounds facilitate the clearance of β-amyloid across the blood-brain barrier. Eur J Pharmacol 2011; 659, 124–129.

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