Perspectives on future Alzheimer therapies: Amyloid-β protofibrils-A new target for immunotherapy with BAN2401 in Alzheimer's disease

Alzheimer's Research and Therapy

Volumn 6, Issue 1, 2014, Pages

  Lannfelt, Lars ^a,b   Möller, Christer ^b   Basun, Hans ^a,b   Osswald, Gunilla ^b   Sehlin, Dag ^a   Satlin, Andrew ^c   Logovinsky, Veronika ^c   Gellerfors, Pär ^b  

^a UPPSALA UNIVERSITY   (Sweden)

^b BioArctic Neuroscience   (Sweden)

^c EISAI INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AAB 003; ABP 102; ACI 24; ADUCANUMAB; AFFITOPE AD02; AFFITOPE AD03; ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN ANTIBODY; AMYLOID BETA PROTEIN[1-42]; AMYLOID BETA PROTOFIBRIL; BAN 2401; BAPINEUZUMAB; CRENEZUMAB; GANTENERUMAB; MONOCLONAL ANTIBODY; NOOTROPIC AGENT; PLACEBO; PONEZUMAB; SAR 228810; SOLANEZUMAB; UB 311; UNCLASSIFIED DRUG; V 950; VANUTIDE CRIDIFICAR;

ALZHEIMER DISEASE; ANTIBODY PRODUCTION; BRAIN HEMORRHAGE; COGNITIVE DEFECT; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TARGETING; EDEMA; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOTHERAPY; MENINGOENCEPHALITIS; NEUROTOXICITY; NONHUMAN; PASSIVE IMMUNIZATION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME; VASOGENIC EDEMA;

EID: 84989182917     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/alzrt246     Document Type: Review

References (59)

1. Wimo A, Prince M: World Alzheimer Report 2010: The Global Economic Impact of Dementia. London, UK: Alzheimer's Disease International; 2010.
2. Glenner GG, Wong CW: Alzheimer's disease and down syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 1984, 122:1131-1135.
3. Hardy J, Selkoe DJ: The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002, 297:353-356.
4. Golde T: The Abhypothesis: leading us to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease. Brain Pathol 2005, 15:84-87.
5. Chartier-Harlin M-C, Crawford F, Houlden H: Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-Amyloid precursor protein gene. Nature 1991, 353:844-846.
6. Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L: A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-Terminus of β-Amyloid. Nat Genet 1992, 1:345-347.
7. Citron M, Oltersdorf T, Haass C, McConlogue L, Hung A, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ: Mutation of the β-Amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 1992, 360:672-674.
8. Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, N?slund J, Lannfelt L: The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation. Nat Neurosci 2001, 4:887-893.
9. Scheuner D, Eckman CB, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi RE, Wasco W, Lannfelt L, Selkoe DJ, Younkin SG: Secreted amyloid β-protein similar to that in senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 1996, 2:864-870.
10. Brouwers N, Sleegers K, Van Broeckhoven C: Molecular genetics of Alzheimer's disease: An update. Ann Med 2008, 40:562-583.
11. Schöll M, Wall A, Thordardottir S, Ferreira D, Bogdanovic N, Langström B, Almkvist O, Graff C, Nordberg A: Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers. Neurology 2012, 79:229-236.
12. Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ: Decreased clearance of CNS β-Amyloid in Alzheimer's disease. Science 2010, 330:1774.
13. Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, Hovte K, Gustafson A, Liu Y, Bhangale T, Graham RR, Huttenlocher J, Bjornsdottir G, Andreassen OA, Jönsson EG, Palotie A, Behrens TW, Magnusson OT, Kong A, Thorsteinsdottir U, Watts RJ, Stefansson K: A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 2012, 488:96-99.
14. Barten D, Meredith JJ, Zaczek R, Houston J, Albright C: Gamma-secretase inhibitors for Alzheimer's disease: balancing efficacy and toxicity. Drugs R D 2006, 7:87-97.
15. Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS, Sethuraman G, Mohs R: A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med 2013, 369:341-350.
16. Martenyi F, Dean R, Lowe S, Nakano M, Monk S, Willis B, Gonzales C, Mergott D: BACE inhibitor LY2886721 safety and central and peripheral PK and PD in healthy subjects (HSs). Alzheimers Dement 2012, 8:P583-P584.
17. Forman M, Palcza J, Tseng J, Leempoels J, Ramael S, Han D, Jhee S, Ereshefsky L, Tanen M, Laterza O, Dockendorf M, Krishna G, MA L, Wagner J, Troyer M: The novel BACE inhibitor MK-8931 dramatically lowers cerebrospinal fluid peptides in healthy subjects following single-And multiple dose administration. Alzheimers Dement 2012, 8:P704.
18. Jeppsson F, Eketjäll S, Janson J, Karlström S, Gustavsson S, Olsson LL, Radesäter AC, Ploeger B, Cebers G, Kolmodin K, Swahn BM, von Berg S, Bueters T, Fälting J: Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer's disease. J Biochem 2012, 287:41245-41257.
19. Gunn AP, Masters CL, Cherny RA: Pyroglutamate-Aβ: role in the natural history of Alzheimer's disease. Int J Biochem Cell Biol 2010, 42:1915-1918.
20. Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM, ELND005-AD201 Investigators: A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology 2011, 77:1253-1262.
21. Aisen PS, Gauthier S, Ferris SH, Saumier D, Haine D, Garceau D, Duong A, Suhy J, Oh J, Lau WC, Sampalis J: Tramiprosate in mild-To-moderate Alzheimer's disease-A randomized, double-blind, placebo-controlled, multicentre study (the Alphase study). Arch Med Sci 2011, 7:102-111.
22. Gilman S, Koller M, Black R, Jenkins L, Griffith S, Fox N, Eisner L, Kirby L, Rovira M, Forette F, Orgogozo J: Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005, 64:1553-1562.
23. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR, Bapineuzumab 301 and 302 Clinical Trial Investigators: Two phase 3 trials of bapineuzumab in mild-To-moderate Alzheimer's disease. N Engl J Med 2014, 370:322-333.
24. Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO: Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: A case report. Nat Med 2003, 9:448-452.
25. Vellas B, Black R, Thal LJ, Fox NC, Daniels M, McLennan G, Tompkins C, Leibman C, Pomfret M, Grundman M: Long-Term follow-up of patients immunized with AN1792: reduced functional decline in antibody responders. Curr Alzheimer Res 2009, 6:144-151.
26. Blennow K, Zetterberg H, Rinne J, Salloway S, Wei J, Black R, Grundman M, Liu E: Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol 2012, 69:1002-1010.
27. Rinne J, Brooks D, Rossor M, Fox N, Bullock R, Klunk W, Mathis C, Blennow K, Barakos J, Okello A, Rodriguez Martinez De Liano S, Liu E, Koller M, Gregg K, Schenk D, Black R, Grundman M: 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer's disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending dose study. Lancet Neurol 2010, 9:363-372.
28. Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Raul SM, Siemers ER: Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimers Dement 2012, 8:261-271.
29. Eli L: Lilly announces detailed results of the phase 3 solanezumab EXPEDITION studies following a presentation of the independent analyses by the Alzheimer's disease Cooperative Study (ADCS). Indianapolis, IN: Lilly; 2012. https://investor. lilly.com/releasedetail.cfm?releaseid=711933.
30. Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, Maguire RP, Blennow K, Lundmark J, Staufenbiel M, Orgogozo JM, Graf A: Safety, tolerability and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease. Randomised, doubleblind, placebo-controlled, first-in-human study. Lancet 2012, 11:597-604.
31. Katzman R: Alzheimer's disease. N Engl J Med 1986, 314:964-973.
32. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R: Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991, 30:572-580.
33. Dickson DW, Chrystal HA, Bevona C, Honer W, Vincent I, Davies P: Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging 1995, 16:285-298.
34. N?slund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P, Buxbaum J: Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline. JAMA 2000, 283:1571-1577.
35. Busciglio J, Lorenzo A, Yankner B: Methological variables in the assessment of β-Amyloid neurotoxicity. Neurobiol Aging 1992, 13:609-612.
36. Pike CJ, Walancewics AJ, Glabe CG, Cotman CW: In vitro aging of β-Amyloid protein causes peptide aggregation and neurotoxicity. Brain Res 1991, 563:311-314.
37. Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB: Amyloid β-protein fibrillogenesis. J Biol Chem 1997, 272:22364-22372.
38. Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, Selkoe DJ: Protofibrillar intermediates of amyloid β-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 1999, 19:8876-8884.
39. O'Nuallain B, Freir DB, Nicoll AJ, Risse E, Ferguson N, Herron CE, Collinge J, Walsh DM: Amyloid β-protein dimers rapidly form stable synaptotoxic protofibrils. J Neurosci 2010, 30:14411-14419.
40. Paranjape GS, Gouwens LK, Osborn DC, Nichols MR: Isolated amyloid-β (1-42) protofibrils, but not isolated fibrils, are robust stimulators of microglia. ACS Chem Neurosci 2012, 3:302-311.
41. McLean C, Cherny R, Fraser F, Fuller S, Smith M, Beyreuther K, Bush A, Masters C: Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 1999, 46:860-866.
42. Lesne S, Koh M, Kotilinek L, Kayed R, Glabe C, Yang A, Gallagher M, Ashe K: A specific amyloid-β protein assembly in the brain impairs memory. Nature 2006, 440:352-357.
43. Englund H, Sehlin D, Johansson A-S, Nilsson LN, Gellerfors P, Paulie S, Lannfelt L, Ekholm Pettersson F: Sensitive ELISA detection of amyloid-β protofibrils in biological samples. J Neurochem 2007, 103:334-345.
44. Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, Lannfelt L, Ekholm Pettersson F: Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation. PLoS One 2012, 7:e32014.
45. Johansson A-S, Berglind Dehlin F, Karlsson G, Edwards K, Gellerfors P, Lannfelt L: Physiochemical characterization of the Alzheimer's disease-related peptides Aβ1-42Arctic and Aβ1-42wt. FEBS J 2006, 273:2618-2630.
46. Sahlin C, Lord A, Magnusson K, Englund H, Almeida CG, Greengard P, Nyberg F, Gouras GK, Lannfelt L, Nilsson LN: The Arctic Alzheimer mutation favors intracellular amyloid-β production by making amyloid precursor protein less available to alpha-secretase. J Neurochem 2007, 101:854-862.
47. Lord A, Kalimo H, Eckman CB, Zhang X-Q, Lannfelt L, Nilsson LN: The Arctic Alzheimer mutation facilitates early intraneuronal Aβ aggregation and senile plaque formation in transgenic mice. Neurobiol Aging 2006, 27:67-77.
48. Knobloch M, Konietzko U, Krebs DC, Nitsch RM: Intracellular Aβ and cognitive deficits precede β-Amyloid deposition in transgenic arcAβ mice. Neurobiol Aging 2007, 28:1297-1306.
49. Lord A, Englund H, Söderberg L, Tucker S, Clausen F, Hillered L, Gordon M, Morgan D, Lannfelt L, Ekholm Pettersson F, Nilsson LN: Amyloid-β protofibril levels correlate with spatial learning in Arctic Alzheimer's disease transgenic mice. FEBS J 2009, 276:995-1006.
50. Lord A, Gumucio A, Englund H, Sehlin D, Screpanti Sundquist V, Söderberg L, Möller C, Gellerfors P, Lannfelt L, Ekholm Pettersson F, Nilsson LN: An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease. Neurobiol Dis 2009, 36:425-434.
51. Jack CRJ, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigland SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ: Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013, 12:207-216.
52. Blennow K, Zetterberg H: The application of cerebrospinal fluid biomarkers in early diagnosis of Alzheimer disease. Med Clin North Am 2013, 97:369-376.
53. Mitchell AJ, Shiri-Feshki M: Rate of progression of mild cognitive impairment to dementia-meta-Analysis of 41 robust inception-cohort studies. Acta Psychiatr Scand 2009, 119:252-265.
54. CTAD: CTAD: New Data on Sola, Bapi, Spark Theragnostics Debate. In New Data on Sola, Bapi, Spark Theragnostics Debate. http://www.alzforum. org/news/conference-coverage/ctad-new-data-sola-bapi-sparktheragnostics-debate.
55. Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Nagren K, Bullock R, Walker Z, Kennedy A, Fox NC, Rossor MN, Rinne JO, Brooks DJ: Conversion of amyloid positive and negative MCI to AD over 3 years: An 11C-PIB PET study. Neurology 2009, 73:754-760.
56. Logovinsky V, Hendrix S, Perdomo C, Wang J, Satlin A: New composite score demonstrates sensitivity to disease progression and treatment effects. Florence, Italy: Paper presented at the 11th International Conference on Alzheimer's and Parkinson's Disease (AD/PD); 2013.
57. Logovinsky V: New Frontier: developing outcome measures for pre-dementia trials. http://www.alzforum.org/webinars/new-frontier-developing-outcomemeasures-pre-dementia-Trials.
58. Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ: Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010, 9:119-128.
59. Satlin A, Logovinsky V, Wang J, Swanson C, Berry S, Berry D: Bayesian adaptive trial design: A new approach for phase 2 clinical trials in Alzheimer's disease. Monte Carlo, Monaco: Paper presented at Clinical Trials in Alzheimer's Disease (CTAD); 2012.