The case for soluble Aβ oligomers as a drug target in Alzheimer's disease

Trends in Pharmacological Sciences

Volumn 34, Issue 5, 2013, Pages 261-266

  Hefti, Franz ^a   Goure, William F ^a   Jerecic, Jasna ^a   Iverson, Kent S ^a   Walicke, Patricia A ^a   Krafft, Grant A ^a  

^a Acumen Pharmaceuticals Inc   (United States)

Author keywords

A fibrils; A derived diffusible ligands; neurodegeneration; synaptic degeneration

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; OLIGOMER;

ALZHEIMER DISEASE; AMYLOID PLAQUE; ANTIGEN BINDING; BINDING AFFINITY; DRUG RESEARCH; DRUG TARGETING; LONG TERM POTENTIATION; NERVE DEGENERATION; NEUROFIBRILLARY TANGLE; NONHUMAN; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CEREBROSPINAL FLUID LEVEL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; SYNAPTIC TRANSMISSION;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; HUMANS; MOLECULAR TARGETED THERAPY;

EID: 84876925888     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2013.03.002     Document Type: Review

References (70)

1. M. Grundman 2012: A watershed year for Alzheimer's disease research J. Nutr. Health Aging 17 2013 51 53
2. T. Oda Clusterin inhibits aggregation of β-amyloid protein and forms a soluble complex that causes oxidative stress Exp. Neurol. 136 1995 22 31
3. 1-42 are potent central nervous system neurotoxins Proc. Natl. Acad. Sci. U.S.A. 95 1998 6448 6453
4. Y-M. Kuo Water-soluble Aβ (N-40, N-42) oligomers in normal and Alzheimer disease brains J. Biol. Chem. 271 1996 4077 4081
5. Y. Gong Alzheimer's disease-affected brain: presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss Proc. Natl. Acad. Sci. U.S.A. 100 2003 10417 10422
6. S. Lesné A specific amyloid-β protein assembly in the brain impairs memory Nat. Lett. 440 2006 352 357
7. D. Sehlin Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation PLoS ONE 7 2012 e32014
8. M. Jin Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce tau hyperphosphorylation and neuritic degeneration Proc. Natl. Acad. Sci. U.S.A. 108 2011 5819 5824
9. I. Benilova The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes Nat. Neurosci. 15 2012 349 357
10. 1-42 oligomers to fibrils Nat. Struct. Mol. Biol. 17 2010 561 567
11. H.S. Hillen Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies J. Neurosci. 30 2010 10369 10379
12. M. Hoshi Spherical aggregates of amyloid β (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase-3β Proc. Natl. Acad. Sci. U.S.A. 100 2003 6370 7375
13. S. Li Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors J. Neurosci. 31 2011 6627 6638
14. W.B. Stine In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis J. Biol. Chem. 278 2003 11612 11622
15. G. Rammes Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of amyloid β oligomers on long-term potentiation (LTP) in murine hippocampal slices Neuropharmacology 60 2011 982 990
16. D.A. Ryan An improved method for generating consistent soluble amyloid-beta oligomer preparations for in vitro neurotoxicity studies J. Neurosci. Methods 190 2010 171 179
17. P.J. Shughrue Anti-ADDL antibodies differentially block oligomer binding to hippocampal neurons Neurobiol. Aging 31 2010 189 202
18. W. Zago Neutralization of soluble, synaptotoxic amyloid β species by antibodies is epitope specific J. Neurosci. 32 2012 2696 2702
19. W.B. Stine Preparing synthetic Aβ in different aggregation states Methods Mol. Biol. 670 2011 13 32
20. 1-42 oligomer - a homogeneous and stable neuropathological protein in Alzheimer's disease J. Neurochem. 95 2005 834 847
21. 1-42 globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents J. Neurosci. 28 2008 788 797
22. B. O'Nuallain A monoclonal antibody against synthetic Aβ dimer assemblies neutralizes brain-derived synaptic plasticity-disrupting Aβ J. Neurochem. 119 2011 189 201
23. M.E. Larson, and S.E. Lesné Soluble Aβ oligomer production and toxicity J. Neurochem. 120 Suppl. 1 2012 125 139
24. I. Klyubin Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo Nat. Med. 11 2005 556 561
25. M. Necula Small molecule inhibitors of aggregation indicate that amyloid β oligomerization and fibrillization pathways are independent and distinct J. Biol. Chem. 282 2007 10311 10324
26. G.P. Gellerman Aβ-globulomers are formed independently of the fibril pathway Neurobiol. Dis. 30 2008 212 220
27. M.D. Kirkitadze Identification and characterization of key kinetic intermediates in amyloid β-protein fibrillogenesis J. Mol. Biol. 312 2001 1103 1119
28. G. Bitan Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways Proc. Natl. Acad. Sci. U.S.A. 100 2003 330 335
29. C.G. Glabe Structural classification of toxic amyloid oligomers J. Biol. Chem. 283 2008 29639 29643
30. S. Lesné Plaque-bearing mice with reduced levels of oligomeric amyloid-β assemblies have intact memory function Neuroscience 151 2008 745 749
31. R.M. Koffie Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques Proc. Natl. Acad. Sci. U.S.A. 106 2009 4012 4017
32. R.C. Gaspar Oligomers of amyloid β are sequestered into and seed new plaques in the brains of an AD mouse model Exp. Neurol. 223 2010 394 400
33. J.R. Cirrito In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-β metabolism and half-life J. Neurosci. 23 2003 8844 8853
34. M. Garcia-Alloza Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575 Mol. Neurodegener. 4 2009 19
35. J.L. Jankowsky Persistent amyloidosis following suppression of Aβ production in a transgenic model of Alzheimer disease PLoS Med. 2 2005 e355
36. D.B. Teplow Elucidating amyloid β-protein folding and assembly: a multidisciplinary approach Acc. Chem. Res. 39 2006 635 645
37. S.W. Snyder Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths Biophys. J. 67 1994 1216 1228
38. I. Klyubin Alzheimer's disease Aβ assemblies mediating rapid disruption of synaptic plasticity and memory Mol. Brain 5 2012 25
39. P.N. Lacor Synaptic targeting by Alzheimer's-related amyloid β oligomers J. Neurosci. 24 2004 10191 10200
40. F.G. De Felice Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers Neurobiol. Aging 29 2008 1334 1347
41. M. Townsend Effects of secreted oligomers of amyloid β-protein on hippocampal synaptic plasticity: a potent role for trimers J. Physiol. 572 2006 477 492
42. Q. Wang Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5 J. Neurosci. 24 2004 3370 3378
43. M.N. Reed Cognitive effects of cell-derived and synthetically derived Aβ oligomers Neurobiol. Aging 32 2011 1784 1794
44. H. Hsieh AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss Neuron 52 2006 831 843
45. G.M. Shankar Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory Nat. Med. 14 2008 837 842
46. P.N. Lacor Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease J. Neurosci. 27 2007 796 807
47. M. Townsend Soluble Aβ inhibits specific signal transduction cascades common to the insulin receptor pathway J. Biol. Chem. 282 2007 33305 33312
48. W. Yu A critical role for the PAR-1/MARK-tau axis in mediating the toxic effects of Aβ on synapses and dendritic spines Hum. Mol. Genet. 21 2012 1384 1390
49. D.B. Freir Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites Nat. Commun. 2 2011 336 340
50. J. Lauren Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers Nature 457 2009 1128 1132
51. A.E. Barry Alzheimer's disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein J. Neurosci. 31 2011 7259 7263
52. M. Cisse Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice J. Neurosci. 31 2011 10427 10431
53. C. Balducci Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein Proc. Natl. Acad. Sci. U.S.A. 107 2010 2295 2300
54. 2+ elevation, missorting of endogenous tau into dendrites, tau phosphorylation, and destruction of microtubules and spines J. Neurosci. 30 2010 11938 11950
55. S.T. Ferreira, and W.L. Klein The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease Neurobiol. Learn. Mem. 96 2012 529 543
56. M. Sakono, and T. Zako Amyloid oligomers: formation and toxicity of Aβ oligomers FEBS J. 277 2010 1348 1358
57. D.M. Walsh, and D.J. Selkoe Aβ oligomers - a decade of discovery J. Neurochem. 101 2007 1172 1184
58. J.A. Hardy, and G.A. Higgins Alzheimer's disease: the amyloid cascade hypothesis Science 256 1992 184 185
59. D.G. Georganopoulou Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease Proc. Natl. Acad. Sci. U.S.A. 102 2005 2273 2276
60. A.A. Wolfe A quantitative assay selective for amyloid oligomer species differentiates cerebrospinal fluid from Alzheimer's disease and age-matched normal Alzheimers Dement. 8 Suppl. 4 2012 278
61. P.D. Mehta Plasma and cerebrospinal fluid levels of amyloid β proteins 1-40 and 1-42 in Alzheimer disease Arch. Neurol. 57 2000 100 105
62. H. Fukumoto High-molecular-weight amyloid β oligomers are elevated in cerebrospinal fluid of Alzheimer patients FASEB J. 24 2010 2716 2726
63. A. Delacourte Nonoverlapping but synergetic tau and APP pathologies in sporadic Alzheimer's disease Neurology 59 2002 398 407
64. G.A. Krafft ACU-193: a drug candidate antibody selectively recognizing soluble Aβ oligomers Abstracts of the 2012 Neuroscience Meeting Planner 2012 Society for Neuroscience Program No. 851.20
65. Look, G.C. et al. Acumen Pharmaceuticals. Methods of inhibiting the formation of amyloid-β diffusible ligands using acylhydrazide compounds, WO/2009/009768
66. S.M. Catalano Receptor antagonists inhibit Aβ oligomer-induced deficits Abstracts of the 2012 Neuroscience Meeting Planner 2012 Society for Neuroscience Program No. 853.11
67. P. Giannokopoulos Pathological substrates of cognitive decline in Alzheimer's disease Front. Neurol. Neurosci. 24 2009 20 29
68. L. Rami Cerebrospinal fluid biomarkers and memory present distinct associations along the continuum from healthy subjects to AD patients J. Alzheimers Dis. 23 2011 319 326
69. R.A. Hansen Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis Clin. Interv. Aging 3 2008 211 225
70. J.C. Dodart Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model Nat. Neurosci. 5 2002 452 457