Tau immunization: A cautionary tale?

Neurobiology of Aging

Volumn 36, Issue 3, 2015, Pages 1316-1332

  Mably, Alexandra J ^a   Kanmert, Daniel ^a   Mc Donald, Jessica M ^a   Liu, Wen ^a   Caldarone, Barbara J ^b   Lemere, Cynthia A ^a   O'Nuallain, Brian ^a   Kosik, Kenneth S ^c   Walsh, Dominic M ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b The Harvard Center for Neurodegeneration & Repair   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alzheimer's disease; APP; Extracellular tau; Tau immunotherapy; Transgenic mice

Indexed keywords

AMYLOID BETA PROTEIN; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 5E2; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY DETECTION; ARTICLE; CONTROLLED STUDY; DRUG BRAIN LEVEL; DRUG EFFICACY; DRUG SAFETY; FEMALE; IMMUNOREACTIVITY; MALE; MORTALITY; MOUSE; NONHUMAN; PASSIVE IMMUNIZATION; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CEREBROSPINAL FLUID LEVEL; PROTEIN CONTENT; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SPATIAL LEARNING; SPATIAL MEMORY; TREATMENT DURATION; ANIMAL; DISEASE MODEL; IMMUNOLOGY; IMMUNOTHERAPY; MEMORY; PSYCHOLOGY; TRANSGENIC MOUSE; TREATMENT FAILURE;

ALZHEIMER DISEASE; ANIMALS; ANTIBODIES, MONOCLONAL; DISEASE MODELS, ANIMAL; FEMALE; IMMUNOTHERAPY; MALE; MEMORY; MICE, TRANSGENIC; TAU PROTEINS; TREATMENT FAILURE;

EID: 84923630766     PISSN: 01974580     EISSN: 15581497     Source Type: Journal    
DOI: 10.1016/j.neurobiolaging.2014.11.022     Document Type: Article

References (105)

1. Ahmed Z., Cooper J., Murray T.K., Garn K., McNaughton E., Clarke H., Parhizkar S., Ward M.A., Cavallini A., Jackson S., Bose S., Clavaguera F., Tolnay M., Lavenir I., Goedert M., Hutton M.L., O'Neill M.J. Anovel invivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity. Acta Neuropathol. 2014, 127:667-683.
2. Ashe K.H. Learning and memory in transgenic mice modeling Alzheimer's disease. Learn Mem. 2001, 8:301-308.
3. Ashe K.H., Zahs K.R. Probing the biology of Alzheimer's disease in mice. Neuron 2010, 66:631-645.
4. Asuni A.A., Boutajangout A., Quartermain D., Sigurdsson E.M. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J.Neurosci. 2007, 27:9115-9129.
5. Ballatore C., Lee V.M., Trojanowski J.Q. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat. Rev. Neurosci. 2007, 8:663-672.
6. Barry A.E., Klyubin I., Mc Donald J.M., Mably A.J., Farrell M.A., Scott M., Walsh D.M., Rowan M.J. Alzheimer's disease brain-derived amyloid-beta-mediated inhibition of LTP invivo is prevented by immunotargeting cellular prion protein. J.Neurosci. 2011, 31:7259-7263.
7. Barten D.M., Cadelina G.W., Hoque N., DeCarr L.B., Guss V.L., Yang L., Sankaranarayanan S., Wes P.D., Flynn M.E., Meredith J.E., Ahlijanian M.K., Albright C.F. Tau transgenic mice as models for cerebrospinal fluid tau biomarkers. J.Alzheimers Dis. 2011, 24(Suppl 2):127-141.
8. Bi M., Ittner A., Ke Y.D., Gotz J., Ittner L.M. Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice. PLoS One 2011, 6:e26860.
9. Binder L.I., Frankfurter A., Rebhun L.I. The distribution of tau in the mammalian central nervous system. J.Cell Biol. 1985, 101:1371-1378.
10. Boimel M., Grigoriadis N., Lourbopoulos A., Haber E., Abramsky O., Rosenmann H. Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice. Exp. Neurol. 2010, 224:472-485.
11. Born H.A., Kim J.Y., Savjani R.R., Das P., Dabaghian Y.A., Guo Q., Yoo J.W., Schuler D.R., Cirrito J.R., Zheng H., Golde T.E., Noebels J.L., Jankowsky J.L. Genetic suppression of transgenic APP rescues hypersynchronous network activity in a mouse model of Alzheimer's disease. J.Neurosci. 2014, 34:3826-3840.
12. Boutajangout A., Ingadottir J., Davies P., Sigurdsson E.M. Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J.Neurochem. 2011, 118:658-667.
13. Boutajangout A., Li Y.S., Quartermain D., Sigurdsson E.M. Cognitive and sensorimotor tasks for assessing functional impairments in mouse models of Alzheimer's disease and related disorders. Methods Mol. Biol. 2012, 849:529-540.
14. Boutajangout A., Quartermain D., Sigurdsson E.M. Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J.Neurosci. 2010, 30:16559-16566.
15. Brion J.P., Guilleminot J., Couchie D., Flament-Durand J., Nunez J. Both adult and juvenile tau microtubule-associated proteins are axon specific in the developing and adult rat cerebellum. Neuroscience 1988, 25:139-146.
16. Burbach G.J., Vlachos A., Ghebremedhin E., Del Turco D., Coomaraswamy J., Staufenbiel M., Jucker M., Deller T. Vessel ultrastructure in APP23 transgenic mice after passive anti-Abeta immunotherapy and subsequent intracerebral hemorrhage. Neurobiol. Aging 2007, 28:202-212.
17. Busciglio J., Lorenzo A., Yeh J., Yankner B.A. Beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron 1995, 14:879-888.
18. Castillo-Carranza D.L., Sengupta U., Guerrero-Munoz M.J., Lasagna-Reeves C.A., Gerson J.E., Singh G., Estes D.M., Barrett A.D., Dineley K.T., Jackson G.R., Kayed R. Passive immunization with tau oligomer monoclonal antibody reverses tauopathy phenotypes without affecting hyperphosphorylated neurofibrillary tangles. J.Neurosci. 2014, 34:4260-4272.
19. Chai X., Dage J.L., Citron M. Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol. Dis. 2012, 48:356-366.
20. Chai X., Wu S., Murray T.K., Kinley R., Cella C.V., Sims H., Buckner N., Hanmer J., Davies P., O'Neill M.J., Hutton M.L., Citron M. Passive immunization with anti-tau antibodies in two transgenic models: reduction of tau pathology and delay of disease progression. J.Biol. Chem. 2011, 286:34457-34467.
21. Chen C., Kim J.J., Thompson R.F., Tonegawa S. Hippocampal lesions impair contextual fear conditioning in two strains of mice. Behav. Neurosci. 1996, 110:1177-1180.
22. Cheng I.H., Palop J.J., Esposito L.A., Bien-Ly N., Yan F., Mucke L. Aggressive amyloidosis in mice expressing human amyloid peptides with the arctic mutation. Nat. Med. 2004, 10:1190-1192.
23. Cheng I.H., Scearce-Levie K., Legleiter J., Palop J.J., Gerstein H., Bien-Ly N., Puolivali J., Lesne S., Ashe K.H., Muchowski P.J., Mucke L. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J.Biol. Chem. 2007, 282:23818-23828.
24. Clavaguera F., Bolmont T., Crowther R.A., Abramowski D., Frank S., Probst A., Fraser G., Stalder A.K., Beibel M., Staufenbiel M., Jucker M., Goedert M., Tolnay M. Transmission and spreading of tauopathy in transgenic mouse brain. Nat. Cell Biol. 2009, 11:909-913.
25. Clavaguera F., Grueninger F., Tolnay M. Intercellular transfer of tau aggregates and spreading of tau pathology: implications for therapeutic strategies. Neuropharmacology 2014, 76 Pt A:9-15.
26. Crabbe J.C., Wahlsten D., Dudek B.C. Genetics of mouse behavior: interactions with laboratory environment. Science 1999, 284:1670-1672.
27. d'Abramo C., Acker C.M., Jimenez H.T., Davies P. Tau passive immunotherapy in mutant P301L mice: antibody affinity versus specificity. PLoS One 2013, 8:e62402.
28. de Calignon A., Polydoro M., Suarez-Calvet M., William C., Adamowicz D.H., Kopeikina K.J., Pitstick R., Sahara N., Ashe K.H., Carlson G.A., Spires-Jones T.L., Hyman B.T. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 2012, 73:685-697.
29. Deipolyi A.R., Fang S., Palop J.J., Yu G.Q., Wang X., Mucke L. Altered navigational strategy use and visuospatial deficits in hAPP transgenic mice. Neurobiol. Aging 2008, 29:253-266.
30. DeMattos R.B., Boone L.I., Hepburn D.L., Parsadainian M., Bryan M.T., Ness D.K., Piroozi K.S., Holtzman D., Bales K.R., Gitter B.D., Paul S.M., Racke M.K. Invitro and invivo characterization of beta-amyloid antibodies binding to cerebral amyloid angiopathy (CAA) and selective exacerbation of CAA-associated micohemorrhage. Neurobiol. Aging 2004, 25(S2):577.
31. Dillon G.M., Qu X., Marcus J.N., Dodart J.C. Excitotoxic lesions restricted to the dorsal CA1 field of the hippocampus impair spatial memory and extinction learning in C57BL/6 mice. Neurobiol. Learn Mem. 2008, 90:426-433.
32. Dodart J.C., Bales K.R., Gannon K.S., Greene S.J., DeMattos R.B., Mathis C., DeLong C.A., Wu S., Wu X., Holtzman D.M., Paul S.M. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat. Neurosci. 2002, 5:452-457.
33. Dujardin S., Lecolle K., Caillierez R., Begard S., Zommer N., Lachaud C., Carrier S., Dufour N., Auregan G., Winderickx J., Hantraye P., Deglon N., Colin M., Buee L. Neuron-to-neuron wild-type tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. Acta Neuropathol. Commun. 2014, 2:14.
34. Games D., Adams D., Alessandrini R., Barbour R., Berthelette P., Blackwell C., Carr T., Clemens J., Donaldson T., Gillespie F., Guido T., Hagopian S., Johnson-wood K., Khan K., Lee M., Leibowitz P., Lieberburg I., Little A., Masliah E., McConlogue L., Montoya-Zavala M., Mucke L., Paganini L., Penniman E., Power M., Schenk D., Seubert P., Snyder B., Soriano F., Tan H., Vitale J., Wadsworth S., Wolozin B., Zhao J. Alzheimer-type neuropathology in transgenic mice over expressing V717F beta-amyloid precursor protein. Nature 1995, 373:523-527.
35. Geula C., Wu C.K., Saroff D., Lorenzo A., Yuan M., Yankner B.A. Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity. Nat. Med. 1998, 4:827-831.
36. Gotz J., Chen F., van Dorpe J., Nitsch R.M. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by abeta 42 fibrils. Science 2001, 293:1491-1495.
37. Gotz J., Ittner A., Ittner L.M. Tau-targeted treatment strategies in Alzheimer's disease. Br. J. Pharmacol. 2012, 165:1246-1259.
38. Haass C., Mandelkow E. Fyn-tau-amyloid: a toxic triad. Cell 2010, 142:356-358.
39. Hampel H., Blennow K., Shaw L.M., Hoessler Y.C., Zetterberg H., Trojanowski J.Q. Total and phosphorylated tau protein as biological markers of Alzheimer's disease. Exp. Gerontol. 2010, 45:30-40.
40. Henderson V.W., Mack W., Williams B.W. Spatial disorientation in Alzheimer's disease. Arch. Neurol. 1989, 46:391-394.
41. Hong S., Quintero-Monzon O., Ostaszewski B.L., Podlisny D.R., Cavanaugh W.T., Yang T., Holtzman D.M., Cirrito J.R., Selkoe D.J. Dynamic analysis of amyloid beta-protein in behaving mice reveals opposing changes in ISF versus parenchymal abeta during age-related plaque formation. J.Neurosci. 2011, 31:15861-15869.
42. Ida N., Hartmann T., Pantel J., Schroder J., Zerfass R., Forstl H., Sandbrink R., Masters C.L., Beyreuther K. Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. J.Biol. Chem. 1996, 271:22908-22914.
43. Ittner L.M., Ke Y.D., Delerue F., Bi M., Gladbach A., van Eersel J., Wolfing H., Chieng B.C., Christie M.J., Napier I.A., Eckert A., Staufenbiel M., Hardeman E., Gotz J. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 2010, 142:387-397.
44. Jicha G.A., Bowser R., Kazam I.G., Davies P. Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau. J.Neurosci. Res. 1997, 48:128-132.
45. Jin M., Shepardson N., Yang T., Chen G., Walsh D., Selkoe D.J. Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce tau hyperphosphorylation and neuritic degeneration. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:5819-5824.
46. Johnson-Wood K., Lee M., Motter R., Hu K., Gordon G., Barbour R., Khan K., Gordon M., Tan H., Games D., Lieberburg I., Schenk D., Seubert P., McConlogue L. Amyloid precursor protein processing and Abeta42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:1550-1555.
47. Kim W., Lee S., Jung C., Ahmed A., Lee G., Hall G.F. Interneuronal transfer of human tau between lamprey central neurons in situ. J.Alzheimers Dis. 2010, 19:647-664.
48. Kontsekova E., Zilka N., Kovacech B., Novak P., Novak M. First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model. Alzheimer's Res. Ther. 2014, 6:44.
49. Kontsekova E., Zilka N., Kovacech B., Skrabana R., Novak M. Identification of structural determinants on tau protein essential for its pathological function - novel therapeutic target for tau immunotherapy in Alzheimer's disease. Alzheimer's Res. Ther. 2014, 6:45.
50. Kornecook T.J., McKinney A.P., Ferguson M.T., Dodart J.C. Isoform-specific effects of apolipoprotein E on cognitive performance in targeted-replacement mice overexpressing human APP. Genes Brain Behav. 2010, 9:182-192.
51. Kosik K.S., Nukina N., Ihara V., Selkoe D.J., Pope A. Tau-specific monoclonal and polyclonal antibodies suggest that tau is a major antigenic component of Alzheimer neurofibrillary tangles (NFT). J.Neuropathol. Exp. Neurol. 1986, 45:378.
52. Ksiezak-Reding H., Binder L.I., Yen S.H. Immunochemical and biochemical characterization of tau proteins in normal and Alzheimer's disease brains with Alz 50 and Tau-1. J.Biol. Chem. 1988, 263:7948-7953.
53. Lalonde R., Fukuchi K., Strazielle C. Neurologic and motor dysfunctions in APP transgenic mice. Rev. Neurosci. 2012, 23:363-379.
54. Lee E.B., Leng L.Z., Zhang B., Kwong L., Trojanowski J.Q., Abel T., Lee V.M. Targeting amyloid-beta peptide (Abeta) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Abeta precursor protein (APP) transgenic mice. J.Biol. Chem. 2006, 281:4292-4299.
55. Levites Y., Das P., Price R.W., Rochette M.J., Kostura L.A., McGowan E.M., Murphy M.P., Golde T.E. Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model. J.Clin. Invest. 2006, 116:193-201.
56. Liu L., Drouet V., Wu J.W., Witter M.P., Small S.A., Clelland C., Duff K. Trans-synaptic spread of tau pathology invivo. PLoS One 2012, 7:e31302.
57. Liu T., Perry G., Chan H.W., Verdile G., Martins R.N., Smith M.A., Atwood C.S. Amyloid-beta-induced toxicity of primary neurons is dependent upon differentiation-associated increases in tau and cyclin-dependent kinase 5 expression. J.Neurochem. 2004, 88:554-563.
58. LoPresti P., Szuchet S., Papasozomenos S.C., Zinkowski R.P., Binder L.I. Functional implications for the microtubule-associated protein tau: localization in oligodendrocytes. Proc. Natl. Acad. Sci. U. S. A. 1995, 92:10369-10373.
59. Maia L.F., Kaeser S.A., Reichwald J., Hruscha M., Martus P., Staufenbiel M., Jucker M. Changes in amyloid-beta and tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci. Transl Med. 2013, 5:194re2.
60. Maier M., Seabrook T.J., Lazo N.D., Jiang L., Das P., Janus C., Lemere C.A. Short amyloid-beta (Abeta) immunogens reduce cerebral Abeta load and learning deficits in an Alzheimer's disease mouse model in the absence of an Abeta-specific cellular immune response. J.Neurosci. 2006, 26:4717-4728.
61. Mc Donald J.M., Cairns N.J., Taylor-Reinwald L., Holtzman D., Walsh D.M. The levels of water-soluble and triton-soluble Abeta are increased in Alzheimer's disease brain. Brain Res. 2012, 1450:138-147.
62. Mercken M., Vandermeeren M., Lubke U., Six J., Boons J., Van de Voorde A., Martin J.J., Gheuens J. Monoclonal antibodies with selective specificity for Alzheimer tau are directed against phosphatase-sensitive epitopes. Acta Neuropathol. 1992, 84:265-272.
63. Mercken M., Vandermeeren M., Lubke U., Six J., Boons J., Vanmechelen E., Van de Voorde A., Gheuens J. Affinity purification of human tau proteins and the construction of a sensitive sandwich enzyme-linked immunosorbent assay for human tau detection. J.Neurochem. 1992, 58:548-553.
64. Meredith J.E., Sankaranarayanan S., Guss V., Lanzetti A.J., Berisha F., Neely R.J., Slemmon J.R., Portelius E., Zetterberg H., Blennow K., Soares H., Ahlijanian M., Albright C.F. Characterization of novel CSF tau and ptau biomarkers for Alzheimer's disease. PLoS One 2013, 8:e76523.
65. Monacelli A.M., Cushman L.A., Kavcic V., Duffy C.J. Spatial disorientation in Alzheimer's disease: the remembrance of things passed. Neurology 2003, 61:1491-1497.
66. Morris M., Maeda S., Vossel K., Mucke L. The many faces of tau. Neuron 2011, 70:410-426.
67. Mucke L., Masliah E., Yu G.Q., Mallory M., Rockenstein E.M., Tatsuno G., Hu K., Kholodenko D., Johnson-Wood K., McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J.Neurosci. 2000, 20:4050-4058.
68. Oddo S., Billings L., Kesslak J.P., Cribbs D.H., LaFerla F.M. Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 2004, 43:321-332.
69. O'Dowd S.T., Ardah M.T., Johansson P., Lomakin A., Benedek G.B., Roberts K.A., Cummins G., El Agnaf O.M., Svensson J., Zetterberg H., Lynch T., Walsh D.M. The ELISA-measured increase in cerebrospinal fluid tau that discriminates Alzheimer's disease from other neurodegenerative disorders is not attributable to differential recognition of tau assembly forms. J.Alzheimers Dis. 2013, 33:923-928.
70. Olton D.S., Samuelson R.J. Remembrance of places passed: spatial memory in rats. J.Exp. Pyschol. Anim. Behav. Process 1976, 2:97-116.
71. Palop J.J., Chin J., Roberson E.D., Wang J., Thwin M.T., Bien-Ly N., Yoo J., Ho K.O., Yu G.Q., Kreitzer A., Finkbeiner S., Noebels J.L., Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 2007, 55:697-711.
72. Palop J.J., Jones B., Kekonius L., Chin J., Yu G.Q., Raber J., Masliah E., Mucke L. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:9572-9577.
73. Park S.Y., Ferreira A. The generation of a 17 kDa neurotoxic fragment: an alternative mechanism by which tau mediates beta-amyloid-induced neurodegeneration. J.Neurosci. 2005, 25:5365-5375.
74. Petry F.R., Pelletier J., Bretteville A., Morin F., Calon F., Hebert S.S., Whittington R.A., Planel E. Specificity of anti-tau antibodies when analyzing mice models of Alzheimer's disease: problems and solutions. PLoS One 2014, 9:e94251.
75. Pfeifer M., Boncristiano S., Bondolfi L., Stalder A., Deller T., Staufenbiel M., Mathews P.M., Jucker M. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science 2002, 298:1379.
76. Phillips R.G., LeDoux J.E. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 1992, 106:274-285.
77. Racke M.M., Boone L.I., Hepburn D.L., Parsadainian M., Bryan M.T., Ness D.K., Piroozi K.S., Jordan W.H., Brown D.D., Hoffman W.P., Holtzman D.M., Bales K.R., Gitter B.D., May P.C., Paul S.M., DeMattos R.B. Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta. J.Neurosci. 2005, 25:629-636.
78. Rapoport M., Dawson H.N., Binder L.I., Vitek M.P., Ferreira A. Tau is essential to beta -amyloid-induced neurotoxicity. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:6364-6369.
79. Rasool S., Martinez-Coria H., Wu J.W., Laferla F., Glabe C.G. Systemic vaccination with anti-oligomeric monoclonal antibodies improves cognitive function by reducing Abeta deposition and tau pathology in 3xTg-AD mice. J.Neurochem. 2013, 142:473-482.
80. Reeves J.P., Lo C.Y., Klinman D.M., Epstein S.L. Mouse monoclonal antibodies to human immunodeficiency virus glycoprotein 120 generated by repeated immunization with glycoprotein 120 from a single isolate, or by sequential immunization with glycoprotein 120 from three isolates. Hybridoma 1995, 14:235-242.
81. Reiber H., Felgenhauer K. Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin. Chim. Acta 1987, 163:319-328.
82. Roberson E.D., Halabisky B., Yoo J.W., Yao J., Chin J., Yan F., Wu T., Hamto P., Devidze N., Yu G.Q., Palop J.J., Noebels J.L., Mucke L. Amyloid-beta/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J.Neurosci. 2011, 31:700-711.
83. Roberson E.D., Scearce-Levie K., Palop J.J., Yan F., Cheng I.H., Wu T., Gerstein H., Yu G.Q., Mucke L. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 2007, 316:750-754.
84. Rosenmann H., Grigoriadis N., Karussis D., Boimel M., Touloumi O., Ovadia H., Abramsky O. Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Arch. Neurol. 2006, 63:1459-1467.
85. Rozenstein-Tsalkovich L., Grigoriadis N., Lourbopoulos A., Nousiopoulou E., Kassis I., Abramsky O., Karussis D., Rosenmann H. Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation. Exp. Neurol. 2013, 248:451-456.
86. Sanchez P.E., Zhu L., Verret L., Vossel K.A., Orr A.G., Cirrito J.R., Devidze N., Ho K., Yu G.Q., Palop J.J., Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:E2895-E2903.
87. Santacruz K., Lewis J., Spires T., Paulson J., Kotilinek L., Ingelsson M., Guimaraes A., DeTure M., Ramsden M., McGowan E., Forster C., Yue M., Orne J., Janus C., Mariash A., Kuskowski M., Hyman B., Hutton M., Ashe K.H. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005, 309:476-481.
88. Schenk D. Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. Nat. Rev. Neurosci. 2002, 3:824-828.
89. Schenk D., Basi G.S., Pangalos M.N. Treatment strategies targeting amyloid beta-protein. Cold Spring Harb. Perspect. Med. 2012, 2:a006387.
90. Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D., Sinha S., Schlossmacher M., Whaley J., Swindlehurst C., et al. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 1992, 359:325-327.
91. Shankar G.M., Leissring M.A., Adame A., Sun X., Spooner E., Masliah E., Selkoe D.J., Lemere C.A., Walsh D.M. Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. Neurobiol. Dis. 2009, 36:293-302.
92. Shipton O.A., Leitz J.R., Dworzak J., Acton C.E., Tunbridge E.M., Denk F., Dawson H.N., Vitek M.P., Wade-Martins R., Paulsen O., Vargas-Caballero M. Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. J.Neurosci. 2011, 31:1688-1692.
93. Spires-Jones T.L., Hyman B.T. The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 2014, 82:756-771.
94. Sydow A., Van der Jeugd A., Zheng F., Ahmed T., Balschun D., Petrova O., Drexler D., Zhou L., Rune G., Mandelkow E., D'Hooge R., Alzheimer C., Mandelkow E.M. Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic tau mutant. J.Neurosci. 2011, 31:2511-2525.
95. Tanzi R.E. The genetics of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2012, 2:a006296.
96. Troquier L., Caillierez R., Burnouf S., Fernandez-Gomez F.J., Grosjean M.E., Zommer N., Sergeant N., Schraen-Maschke S., Blum D., Buee L. Targeting phospho-Ser422 by active tau immunotherapy in the THYTau22 mouse model: a suitable therapeutic approach. Curr. Alzheimer Res. 2012, 9:397-405.
97. Vossel K.A., Zhang K., Brodbeck J., Daub A.C., Sharma P., Finkbeiner S., Cui B., Mucke L. Tau reduction prevents Abeta-induced defects in axonal transport. Science 2010, 330:198.
98. Wagshal D., Sankaranarayanan S., Guss V., Hall T., Berisha F., Lobach I., Karydas A., Voltarelli L., Scherling C., Heuer H., Tartaglia M.C., Miller Z., Coppola G., Ahlijanian M., Soares H., Kramer J.H., Rabinovici G.D., Rosen H.J., Miller B.L., Meredith J., Boxer A.L. Divergent CSF tau alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J.Neurol. Neurosurg. Psychiatry 2014, published online first: June 4, 2014.
99. Wahlsten D., Metten P., Phillips T.J., Boehm S.L., Burkhart-Kasch S., Dorow J., Doerksen S., Downing C., Fogarty J., Rodd-Henricks K., Hen R., McKinnon C.S., Merrill C.M., Nolte C., Schalomon M., Schlumbohm J.P., Sibert J.R., Wenger C.D., Dudek B.C., Crabbe J.C. Different data from different labs: lessons from studies of gene-environment interaction. J.Neurobiol. 2003, 54:283-311.
100. Walls K.C., Ager R.R., Vasilevko V., Cheng D., Medeiros R., LaFerla F.M. p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice. Neurosci. Lett. 2014, 575:96-100.
101. Wenk G.L. Assessment of spatial memory using the radial arm maze and Morris water maze. Curr. Protoc. Neurosci. 2004, 26. 8.5A:8.5A.1-8.5A.12.
102. Wilcock D.M., Rojiani A., Rosenthal A., Subbarao S., Freeman M.J., Gordon M.N., Morgan D. Passive immunotherapy against Abeta in aged APP-transgenicmice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J.Neuroinflammation 2004, 1:24.
103. Yamada K., Cirrito J.R., Stewart F.R., Jiang H., Finn M.B., Holmes B.B., Binder L.I., Mandelkow E.M., Diamond M.I., Lee V.M., Holtzman D.M. Invivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J.Neurosci. 2011, 31:13110-13117.
104. Yanamandra K., Kfoury N., Jiang H., Mahan T.E., Ma S., Maloney S.E., Wozniak D.F., Diamond M.I., Holtzman D.M. Anti-tau antibodies that block tau aggregate seeding invitro markedly decrease pathology and improve cognition invivo. Neuron 2013, 80:402-414.
105. Zago W., Buttini M., Comery T.A., Nishioka C., Gardai S.J., Seubert P., Games D., Bard F., Schenk D., Kinney G.G. Neutralization of soluble, synaptotoxic amyloid beta species by antibodies is epitope specific. J.Neurosci. 2012, 32:2696-2702.