Amyloid-beta immunotherapy: the hope for Alzheimer disease?
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Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.
- Amyloid beta-Peptides
- antibodies
- cognitive dysfunction
- Alzheimer disease
- adult
- Immunotherapy
- Vaccination
- Immunization
Ali G-C, Guerchet M, Wu Y-T, Prince M, Prina M. Chapter 2: The global prevalence of dementia Prince M, Wimo A, Guerchet M, Ali G-C, Wu Y-T, Prina M. World Alzheimer Report 2015. The Global Impact of Dementia. An analysis of prevalence, incidence, cost and trends. Alzheimer's Disease International (ADI):; London: 2015. p. 10–29
Alzheimer's Association. Special Report: The personal financial impact of Alzheimer's on families Alzheimer's Association. 2016 Alzheimer's Disease Facts and Figures. Chicago: Alzheimer's Association; 2016. p. 58–67. https://www.alz.org/documents_custom/2016-facts-and-figures.pdf
WHO. The Epidemiology and Impact of Dementia: Current state and future trends. 2015. WHO/MSD/MER/15.3. p. 4. http://www.who.int/mental_health/neurology/dementia/dementia_thematicbrief_epidemiology.pdf
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH. The diagnosis of dementia due to Alzheimer's disease recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263–269 DOI: https://doi.org/10.1016/j.jalz.2011.03.005
van der Flier WM.Pijnenburg YA.Fox NC.Scheltens P. Early-onset versus late-onset Alzheimer's disease the case of the missing APOE ?4 allele. Lancet Neurol. 2011;10(3):280–288 DOI: https://doi.org/10.1016/S1474-4422(10)70306-9
Lautenschlager NT, Cupples LA, Rao VS, Auerbach SA, Becker R, Burke J. Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study What is in store for the oldest old? Neurology. 1996;46(3):641–650 DOI: https://doi.org/10.1212/WNL.46.3.641
Coon KD, Myers AJ, Craig DW, Webster JA, Pearson JV, Lince DH. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. J Clin Psychiatry. 2007;68(4):613–618 DOI: https://doi.org/10.4088/JCP.v68n0419
Scarabino D, Broggio E, Gambina G, Maida C, Gaudio MR, Corbo RM. Apolipoprotein E genotypes and plasma levels in mild cognitive impairment conversion to Alzheimer's disease A follow-up study. Am J Med Genet B Neuropsychiatr Genet. 2016;171(8):1131–1138 DOI: https://doi.org/10.1002/ajmg.b.32495
Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kåreholt I, Winblad B. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. 2005;62(10):1556–1560 DOI: https://doi.org/10.1001/archneur.62.10.1556
Li W, Risacher SL, McAllister TW, Saykin AJ. Traumatic brain injury and age at onset of cognitive impairment in older adults. J Neurol. 2016;263(7):1280–1285 DOI: https://doi.org/10.1007/s00415-016-8093-4
Killin LO, Starr JM, Shiue IJ, Russ TC. Environmental risk factors for dementia a systematic review. BMC Geriatr. 2016;16(1):175 DOI: https://doi.org/10.1186/s12877-016-0342-y
Villemagne VL, Pike KE, Chételat G, Ellis KA, Mulligan RS, Bourgeat P. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69(1):181–192 DOI: https://doi.org/10.1002/ana.22248
Saint-Aubert L, Almkvist O, Chiotis K, Almeida R, Wall A, Nordberg A. Regional tau deposition measured by [(18)F]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer's disease. Alzheimers Res Ther. 2016;8(1):38 DOI: https://doi.org/10.1186/s13195-016-0204-z
James OG, Doraiswamy PM, Borges-Neto S. PET Imaging of Tau Pathology in Alzheimer's Disease and Tauopathies. Front Neurol. 2015;6:38 DOI: https://doi.org/10.3389/fneur.2015.00038
Perl DP. Neuropathology of Alzheimer's disease. Mt Sinai J Med. 2010;77(1):32–42 DOI: https://doi.org/10.1002/msj.20157
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595–608 DOI: https://doi.org/10.15252/emmm.201606210
Wilcock GK, Esiri MM. Plaques, tangles and dementia A quantitative study. J Neurol Sci. 1982;56(2-3):343–356 DOI: https://doi.org/10.1016/0022-510X(82)90155-1
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259 DOI: https://doi.org/10.1007/BF00308809
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A. 1998;95(11):6448–6453 DOI: https://doi.org/10.1073/pnas.95.11.6448
Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007;8(2):101–112 DOI: https://doi.org/10.1038/nrm2101
Walsh DM, Selkoe DJ. A beta oligomers - a decade of discovery. J Neurochem. 2007;101(5):1172–1184 DOI: https://doi.org/10.1111/j.1471-4159.2006.04426.x
Thal DR, Rüb U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58(12):1791–1800 DOI: https://doi.org/10.1212/WNL.58.12.1791
Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF. Molecular, structural, and functional characterization of Alzheimer's disease evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25(34):7709–7717 DOI: https://doi.org/10.1523/JNEUROSCI.2177-05.2005
Braak H, Del Tredici K. The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol. 2011;121(2):171–181 DOI: https://doi.org/10.1007/s00401-010-0789-4
Selkoe 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 N Y Acad Sci. 2000;924:17–25 DOI: https://doi.org/10.1111/j.1749-6632.2000.tb05554.x
Zhang H, Ma Q, Zhang YW, Xu H. Proteolytic processing of Alzheimer's β-amyloid precursor protein. J Neurochem. 2012;120 1:9–21 DOI: https://doi.org/10.1111/j.1471-4159.2011.07519.x
Lee J, Retamal C, Cuitiño L, Caruano-Yzermans A, Shin JE, van Kerkhof P. Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. J Biol Chem. 2008;283(17):11501–11508 DOI: https://doi.org/10.1074/jbc.M800642200
Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K. Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci U S A. 1990;87(4):1561–1565 DOI: https://doi.org/10.1073/pnas.87.4.1561
Ehehalt R, Keller P, Haass C, Thiele C, Simons K. Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol. 2003;160(1):113–123 DOI: https://doi.org/10.1083/jcb.200207113
Thinakaran G, Koo EH. Amyloid precursor protein trafficking, processing, and function. J Biol Chem. 2008;283(44):29615–29619 DOI: https://doi.org/10.1074/jbc.R800019200
Fahrenholz F, Gilbert S, Kojro E, Lammich S, Postina R. Alpha-secretase activity of the disintegrin metalloprotease ADAM 10 Influences of domain structure. Ann N Y Acad Sci. 2000;920:215–222 DOI: https://doi.org/10.1111/j.1749-6632.2000.tb06925.x
Asai M, Hattori C, Szabó B, Sasagawa N, Maruyama K, Tanuma S. Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Biochem Biophys Res Commun. 2003;301(1):231–235 DOI: https://doi.org/10.1016/S0006-291X(02)02999-6
Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T. Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science. 1990;248(4959):1122–1124 DOI: https://doi.org/10.1126/science.2111583
Zhang YW, Thompson R, Zhang H, Xu H. APP processing in Alzheimer's disease. Mol Brain. 2011;4:3 DOI: https://doi.org/10.1186/1756-6606-4-3
Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999;286(5440):735–741 DOI: https://doi.org/10.1126/science.286.5440.735
Selkoe DJ, Wolfe MS. Presenilin running with scissors in the membrane. Cell. 2007;131(2):215–221 DOI: https://doi.org/10.1016/j.cell.2007.10.012
St George-Hyslop P, Fraser PE. Assembly of the presenilin -/ε-secretase complex. J Neurochem. 2012;120 1:84–88 DOI: https://doi.org/10.1111/j.1471-4159.2011.07505.x
Mori H, Takio K, Ogawara M, Selkoe DJ. Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. J Biol Chem. 1992;267(24):17082–17086 DOI: https://doi.org/10.1016/S0021-9258(18)41896-0
Serra-Batiste M, Ninot-Pedrosa M, Bayoumi M, Gairí M, Maglia G, Carulla N. Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments. Proc Natl Acad Sci U S A. 2016;113(39):10866–10871 DOI: https://doi.org/10.1073/pnas.1605104113
Walsh DM, Hartley DM, Kusumoto Y, Fezoui Y, Condron MM, Lomakin A. Amyloid beta-protein fibrillogenesis Structure and biological activity of protofibrillar intermediates. J Biol Chem. 1999;274(36):25945–25952 DOI: https://doi.org/10.1074/jbc.274.36.25945
Harper JD, Wong SS, Lieber CM, Lansbury PT. Assembly of A beta amyloid protofibrils an in vitro model for a possible early event in Alzheimer's disease. Biochemistry. 1999;38(28):8972–8980 DOI: https://doi.org/10.1021/bi9904149
Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M. Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio. EMBO J. 2010;29(19):3408–3420 DOI: https://doi.org/10.1038/emboj.2010.211
Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ. Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci. 2011;31(18):6627–6638 DOI: https://doi.org/10.1523/JNEUROSCI.0203-11.2011
Yang TT, Hsu CT, Kuo YM. Cell-derived soluble oligomers of human amyloid-beta peptides disturb cellular homeostasis and induce apoptosis in primary hippocampal neurons. J Neural Transm (Vienna). 2009;116(12):1561–1569 DOI: https://doi.org/10.1007/s00702-009-0311-0
Bertram L, Tanzi RE. Alzheimer's disease: one disorder, too many genes? Hum Mol Genet. 2004;13 Spec No 1:R135–R141 DOI: https://doi.org/10.1093/hmg/ddh077
Goate A, Hardy J. Twenty years of Alzheimer's disease-causing mutations. J Neurochem. 2012;120 1:3–8 DOI: https://doi.org/10.1111/j.1471-4159.2011.07575.x
Cruchaga C, Haller G, Chakraverty S, Mayo K, Vallania FL, Mitra RD. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS One. 2012;7(2):e31039 DOI: https://doi.org/10.1371/journal.pone.0031039
Larner AJ, Doran M. Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene. J Neurol. 2006;253(2):139–158 DOI: https://doi.org/10.1007/s00415-005-0019-5
Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat Med. 1997;3(1):67–72 DOI: https://doi.org/10.1038/nm0197-67
Lopera F, Ardilla A, Martínez A, Madrigal L, Arango-Viana JC, Lemere CA. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA. 1997;277(10):793–799 DOI: https://doi.org/10.1001/jama.277.10.793
Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, Jaramillo-Elorza MC, Moreno S, Aguirre-Acevedo DC. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease a retrospective cohort study. Lancet Neurol. 2011;10(3):213–220 DOI: https://doi.org/10.1016/S1474-4422(10)70323-9
Sherrington R, Froelich S, Sorbi S, Campion D, Chi H, Rogaeva EA. Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant. Hum Mol Genet. 1996;5(7):985–988 DOI: https://doi.org/10.1093/hmg/5.7.985
Jayadev S, Leverenz JB, Steinbart E, Stahl J, Klunk W, Yu CE. Alzheimer's disease phenotypes and genotypes associated with mutations in presenilin 2. Brain. 2010;133(4):1143–1154 DOI: https://doi.org/10.1093/brain/awq033
Lindquist SG, Hasholt L, Bahl JM, Heegaard NH, Andersen BB, Nørremølle A. A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment. Eur J Neurol. 2008;15(10):1135–1139 DOI: https://doi.org/10.1111/j.1468-1331.2008.02256.x
Vélez JI, Lopera F, Patel HR, Johar AS, Cai Y, Rivera D. Mutations modifying sporadic Alzheimer's disease age of onset. Am J Med Genet B Neuropsychiatr Genet. 2016;171(8):1116–1130 DOI: https://doi.org/10.1002/ajmg.b.32493
Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, MacArthur LH. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014;20(4):415–418 DOI: https://doi.org/10.1038/nm.3466
Lachén-Montes M, González-Morales A, de Morentin XM, Pérez-Valderrama E, Ausín K, Zelaya MV. An early dysregulation of FAK and MEK/ERK signaling pathways precedes the β-amyloid deposition in the olfactory bulb of APP/PS1 mouse model of Alzheimer's disease. J Proteomics. 2016;148:149–158 DOI: https://doi.org/10.1016/j.jprot.2016.07.032
Sorbi S, Hort J, Erkinjuntti T, Fladby T, Gainotti G, Gurvit H. EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol. 2012;19(9):1159–1179 DOI: https://doi.org/10.1111/j.1468-1331.2012.03784.x
Ihl R, Bunevicius R, Frölich L, Winblad B, Schneider LS, Dubois B. World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of dementias in primary care. Int J Psychiatry Clin Pract. 2015;19(1):2–7 DOI: https://doi.org/10.3109/13651501.2014.961931
Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M. Effectiveness of cholinesterase inhibitors and memantine for treating dementia evidence review for a clinical practice guideline. Ann Intern Med. 2008;148(5):379–397 DOI: https://doi.org/10.7326/0003-4819-148-5-200803040-00009
Cummings JL, Isaacson RS, Schmitt FA, Velting DM. A practical algorithm for managing Alzheimer's disease what, when, and why? Ann Clin Transl Neurol. 2015;2(3):307–323 DOI: https://doi.org/10.1002/acn3.166
Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006;(1):CD005593 DOI: https://doi.org/10.1002/14651858.CD005593
McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;(2):CD003154 DOI: https://doi.org/10.1002/14651858.CD003154.pub5
Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M. Effect of vitamin E and memantine on functional decline in Alzheimer disease the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311(1):33–44 DOI: https://doi.org/10.1001/jama.2013.282834
Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology. 2003;61(1):46–54 DOI: https://doi.org/10.1212/01.WNL.0000073623.84147.A8
Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, Jenkins L. Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD. Neurology. 2005;64(1):94–101 DOI: https://doi.org/10.1212/01.WNL.0000148604.77591.67
Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64(9):1553–1562 DOI: https://doi.org/10.1212/01.WNL.0000159740.16984.3C
Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T. Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol. 2012;11(7):597–604 DOI: https://doi.org/10.1016/S1474-4422(12)70140-0
Farlow MR, Andreasen N, Riviere ME, Vostiar I, Vitaliti A, Sovago J. Long-term treatment with active Aβ immunotherapy with CAD106 in mild Alzheimer's disease. Alzheimers Res Ther. 2015;7(1):23 DOI: https://doi.org/10.1186/s13195-015-0108-3
Muhs A, Hickman DT, Pihlgren M, Chuard N, Giriens V, Meerschman C. Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc Natl Acad Sci U S A. 2007;104(23):9810–9815 DOI: https://doi.org/10.1073/pnas.0703137104
Morrone CD, Liu M, Black SE, McLaurin J. Interaction between therapeutic interventions for Alzheimer's disease and physiological Aβ clearance mechanisms. Front Aging Neurosci. 2015;7:64 DOI: https://doi.org/10.3389/fnagi.2015.00064
Lichtlen P, Mohajeri MH. Antibody-based approaches in Alzheimer's research safety, pharmacokinetics, metabolism, and analytical tools. J Neurochem. 2008;104(4):859–874 DOI: https://doi.org/10.1111/j.1471-4159.2007.05064.x
Booth CM, Tannock IF. Randomised controlled trials and population-based observational research partners in the evolution of medical evidence. Br J Cancer. 2014;110(3):551–555 DOI: https://doi.org/10.1038/bjc.2013.725
Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci U S A. 1997;94(4):1550–1555 DOI: https://doi.org/10.1073/pnas.94.4.1550
Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73(24):2061–2070 DOI: https://doi.org/10.1212/WNL.0b013e3181c67808
Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE. 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(4):363–372 DOI: https://doi.org/10.1016/S1474-4422(10)70043-0
La Porte SL, Bollini SS, Lanz TA, Abdiche YN, Rusnak AS, Ho WH. Structural basis of C-terminal β-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer's disease. J Mol Biol. 2012;421(4-5):525–536 DOI: https://doi.org/10.1016/j.jmb.2011.11.047
Landen JW, Zhao Q, Cohen S, Borrie M, Woodward M, Billing CB. Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol. 2013;36(1):14–23 DOI: https://doi.org/10.1097/WNF.0b013e31827db49b
Miyoshi I, Fujimoto Y, Yamada M, Abe S, Zhao Q, Cronenberger C. Safety and pharmacokinetics of PF-04360365 following a single-dose intravenous infusion in Japanese subjects with mild-to-moderate Alzheimer's disease a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study. Int J Clin Pharmacol Ther. 2013;51(12):911–923 DOI: https://doi.org/10.5414/CP201816
DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2001;98(15):8850–8855 DOI: https://doi.org/10.1073/pnas.151261398
Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370(4):311–321 DOI: https://doi.org/10.1056/NEJMoa1312889
Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H. Phase 3 solanezumab trials Secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. 2016;12(2):110–120 DOI: https://doi.org/10.1016/j.jalz.2015.06.1893
Carlson C, Siemers E, Hake A, Case M, Hayduk R, Suhy J. Amyloid-related imaging abnormalities from trials of solanezumab for Alzheimer's disease. Alzheimers Dement (Amst). 2016;2:75–85 DOI: https://doi.org/10.1016/j.dadm.2016.02.004
Abbott A, Dolgin E. Failed Alzheimer's trial does not kill leading theory of disease. Nature. 2016;540(7631):15–16 DOI: https://doi.org/10.1038/nature.2016.21045
Bohrmann B, Baumann K, Benz J, Gerber F, Huber W, Knoflach F. Gantenerumab a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers. Dis. 2012;28(1):49–69 DOI: https://doi.org/10.3233/JAD-2011-110977
Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198–207 DOI: https://doi.org/10.1001/archneurol.2011.1538
Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature. 2016;537(7618):50–56 DOI: https://doi.org/10.1038/nature19323
Kastanenka KV, Bussiere T, Shakerdge N, Qian F, Weinreb PH, Rhodes K, et al.. Immunotherapy with aducanumab restores calcium homeostasis in Tg2576 mice. J Neurosci. 2016;36(50):12549–12558 DOI: https://doi.org/10.1523/JNEUROSCI.2080-16.2016
Adolfsson O, Pihlgren M, Toni N, Varisco Y, Buccarello AL, Antoniello K. An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ J. Neurosci. 2012;32(28):9677–9689 DOI: https://doi.org/10.1523/JNEUROSCI.4742-11.2012
Ayutyanont N, Langbaum JB, Hendrix SB, Chen K, Fleisher AS, Friesenhahn M. The Alzheimer's prevention initiative composite cognitive test score sample size estimates for the evaluation of preclinical Alzheimer's disease treatments in presenilin 1 E280A mutation carriers. J Clin Psychiatry. 2014;75(6):652–660 DOI: https://doi.org/10.4088/JCP.13m08927
Tucker S, Möller C, Tegerstedt K, Lord A, Laudon H, Sjödahl J. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43(2):575–588 DOI: https://doi.org/10.3233/JAD-140741
Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G. Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody. Alzheimers Res Ther. 2016;8(1):14 DOI: https://doi.org/10.1186/s13195-016-0181-2
Qu J, Yu S, Zheng Y, Yang H, Zhang J. Aptamer and its applications in neurodegenerative diseases. Cell Mol Life Sci. 2016; DOI: https://doi.org/10.1007/s00018-016-2345-4
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