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Is targeting beta-amyloid pathology, with immunotherapy, an effective treatment option for Alzheimer's disease?

Published online by Cambridge University Press:  25 May 2011

James O'Donovan*
Affiliation:
Medical School, University of Newcastle upon Tyne, UK
*
Address for correspondence: James O'Donovan, 3 Creskeld Crescent, Bramhope, Leeds LS16 9EH. Email: james.o'donovan@ncl.ac.uk

Summary

Alzheimer's disease (AD) is the commonest form of dementia, estimated to affect 37 million people worldwide. Currently there is nothing to halt the progression of AD – treatment focuses largely on slowing the development of symptoms. More recently disease-modifying interventions, such as immunotherapy, have been investigated as their aim is to halt or even reverse symptoms by removing β-amyloid (Aβ) pathology. This paper assesses the developments made in this particular field, offers critical appraisal of important papers and assesses the viability of this potential form of treatment.

Type
Neuropsychiatry of old age
Copyright
Copyright © Cambridge University Press 2011

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References

1Caraci, F, Copani, A, Nicoletti, F, Drago, F. Depression and Alzheimer's disease: Neurobiological links and common pharmacological targets. Eur J Pharmacol 2010; 626: 6471.CrossRefGoogle ScholarPubMed
2BUPA. Alzheimer's disease factsheet. 2009. Available at: http://hcd2.bupa.co.uk/fact_sheets/html/alzheimers_disease.html (accessed 21 February 2010).Google Scholar
3Dawbarn, D, Allen, SJ. Neurobiology of Alzheimer's Disease: Molecular and Cellular Neurobiology, 3rd edn. Oxford; New York: Oxford University Press, 2007.CrossRefGoogle Scholar
4Alzheimer's Society. What is Alzheimer's disease? 2009. Available at: http://alzheimers.org.uk/factsheet/401 (accessed 13 March 2010).Google Scholar
5Lleo, A, Greenberg, SM, Growdon, JH. Current pharmacotherapy for Alzheimer's disease. Ann Rev Med 2006; 57: 513–33.CrossRefGoogle ScholarPubMed
6US Dept of Health and Human Services. Alzheimer's Disease Medications. National Institute of Aging, ed. 2008.Google Scholar
7Hardy, J, Selkoe, DJ. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002; 297: 353–56.CrossRefGoogle ScholarPubMed
8Selkoe, DJ. Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid Beta-protein. Ann New York Acad Sci 2000; 924: 1725.CrossRefGoogle Scholar
9Schenk, 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: 173–77.CrossRefGoogle ScholarPubMed
10Janus, C, Pearson, J, McLaurin, J, Mathews, PM, Jiang, Y, Schmidt, SD, Chishti, MA, Horne, P, Heslin, D, French, J, Mount, HT, Nixon, RA, Mercken, M, Bergeron, C, Fraser, PE, St George-Hyslop, P, Westaway, D. A-beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 2000; 408: 979–82.CrossRefGoogle Scholar
11Bayer, AJ, Bullock, R, Jones, RW, Wilkinson, D, Paterson, KR, Jenkins, L, Millais, SB, Donoghue, S. Evaluation of the safety and immunogenicity of synthetic Aβ 42(AN1792) in patients with AD. Neurology 2005; 64: 94101.CrossRefGoogle Scholar
12Gilman, S, Koller, M, Black, RS, Jenkins, L, Griffith, SG, Fox, NC, Eisner, L, Kirby, L, Rovira, MB, Forette, F, Orgogozo, JM; AN1792(QS-21)-201 Study Team. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005; 64: 1553–62.CrossRefGoogle Scholar
13Orgogozo, JM, Gilman, S, Dartigues, JF, Laurent, B, Puel, M, Kirby, LC, Jouanny, P, Dubois, B, Eisner, L, Flitman, S, Michel, BF, Boada, M, Frank, A, Hock, C. Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization. Neurology 2003; 61: 654.CrossRefGoogle Scholar
14Fox, NC, Black, RS, Gilman, S, Rossor, MN, Griffith, SG, Jenkins, L, Koller, M; AN1792(QS-21)-201 Study. Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 2005; 64: 1563–72.CrossRefGoogle ScholarPubMed
15Weksler, ME. The immunotherapy of Alzheimer's disease. Immunity Ageing 2004; 1: 2.CrossRefGoogle ScholarPubMed
16Holmes, C, Boche, D, Wilkinson, D, Yadegarfar, G, Hopkins, V, Bayer, A, Jones, RW, Bullock, R, Love, S, Neal, JW, Zotova, E, Nicoll, JA. Long-term effects of Abeta-42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 2008; 372: 216–23.CrossRefGoogle ScholarPubMed
17Foster, JK, Verdile, G, Bates, KA, Martins, RN. Immunization in Alzheimer's disease: Naive hope or realistic clinical potential? Mol Psychiat 2009; 14: 239–51.CrossRefGoogle ScholarPubMed
18Istrin, G, Bosis, E, Solomon, B. Intravenous immunoglobulin enhances the clearance of fibrillar amyloid-beta peptide. J Neurosci Res 2006; 84: 434–43.CrossRefGoogle ScholarPubMed
19Bard, F, Cannon, C, Barbour, R, Burke, RL, Games, D, Grajeda, H, Guido, T, Hu, K, Huang, J, Johnson-Wood, K, Khan, K, Kholodenko, D, Lee, M, Lieberburg, I, Motter, R, Nguyen, M, Soriano, F, Vasquez, N, Weiss, K, Welch, B, Seubert, P, Schenk, D, Yednock, T. Peripherally administered antibodies against amyloid Beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med 2000; 6: 916–19.CrossRefGoogle Scholar
20Dodel, RC, Du, Y, Depboylu, C, Hampel, H, Frölich, L, Haag, A, Hemmeter, U, Paulsen, S, Teipel, SJ, Brettschneider, S, Spottke, A, Nölker, C, Möller, HJ, Wei, X, Farlow, M, Sommer, N, Oertel, WH. Intravenous immunoglobulins containing antibodies against Beta-amyloid for the treatment of Alzheimer's disease. J Neurol Neurosurg Psychiat 2004; 75: 1472–74.CrossRefGoogle ScholarPubMed
21Relkin, NR, Szabo, P, Adamiak, B, Burgut, T, Monthe, C, Lent, RW, Younkin, S, Younkin, L, Schiff, R, Weksler, ME. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009; 30: 1728–36.CrossRefGoogle ScholarPubMed
22Salloway, S, Sperling, R, Gilman, S, Fox, NC, Blennow, K, Raskind, M, Sabbagh, M, Honig, LS, Doody, R, van Dyck, CH, Mulnard, R, Barakos, J, Gregg, KM, Liu, E, Lieberburg, I, Schenk, D, Black, R, Grundman, M; Bapineuzumab 201 Clinical Trial Investigators. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009; 73: 2061–70.CrossRefGoogle ScholarPubMed
23Hawkes, CA, McLaurin, J. Clinical immunotherapy trials in Alzheimer's disease. Drug Discovery Today: Therapeutic Strategies 2008; 5: 177–83.Google Scholar
24Rinne, JO, Brooks, DJ, Rossor, MN, Fox, NC, Bullock, R, Klunk, WE, Mathis, CA, Blennow, K, Barakos, J, Okello, AA, Rodriguez Martinez de Liano, S, Liu, E, Koller, M, Gregg, KM, Schenk, D, Black, R, Grundman, M. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 2010; 9: 363–72.CrossRefGoogle ScholarPubMed
25Town, T. Alternative A-Beta immunotherapy approaches for Alzheimer's disease. CNS and Neurological Disorders – Drug Targets 2009; 8: 114–27.CrossRefGoogle Scholar
26Brody, DL, Holtzman, DM. Active and passive immunotherapy for neurodegenerative disorders. Ann Rev Neurosci 2008; 31: 175–93.CrossRefGoogle ScholarPubMed