Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and Amyloid-β Pathologies in 3xTg Mice

Scientific Reports

Volumn 7, Issue 1, 2017, Pages

  Rajamohamedsait, Hameetha ^a   Rasool, Suhail ^a   Rajamohamedsait, Wajitha ^a   Lin, Yan ^a   Sigurdsson, Einar M ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; IMMUNOGLOBULIN G; PRESENILIN 1; TAU PROTEIN;

ALZHEIMER DISEASE; ANIMAL; BLOOD; C57BL MOUSE; CHEMISTRY; DISEASE MODEL; FEMALE; GENETICS; HIPPOCAMPAL CA1 REGION; IMAGE PROCESSING; IMMUNOLOGY; IMMUNOTHERAPY; MALE; MAZE TEST; METABOLISM; MOUSE; PATHOLOGY; TRANSGENIC MOUSE; VACCINATION;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; CA1 REGION, HIPPOCAMPAL; DISEASE MODELS, ANIMAL; FEMALE; IMAGE PROCESSING, COMPUTER-ASSISTED; IMMUNOGLOBULIN G; IMMUNOTHERAPY; MALE; MAZE LEARNING; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PRESENILIN-1; TAU PROTEINS; VACCINATION;

EID: 85038110798     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-017-17313-1     Document Type: Article

References (57)

1. Grundke-Iqbal, I. et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA 83, 4913-4917 (1986).
2. Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol. Med. 8, 595-608 (2016).
3. Braak, H., Thal, D. R., Ghebremedhin, E. & Del, T. K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J. Neuropathol. Exp. Neurol. 70, 960-969 (2011).
4. Congdon, E. E., Krishnaswamy, S. & Sigurdsson, E. M. Harnessing the immune system for treatment and detection of tau pathology. J. Alzheimers. Dis. 40, S113-S121 (2014).
5. 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. 27, 9115-9129 (2007).
6. Boimel, M. et al. Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice. Exp. Neurol. 224, 472-485 (2010).
7. Boutajangout, A., Quartermain, D. & Sigurdsson, E. M. Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J. Neurosci. 30, 16559-16566 (2010).
8. 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. 118, 658-667 (2011).
9. Chai, X. et al. Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression. J. Biol Chem. 286, 34457-34467 (2011).
10. Krishnamurthy, P. K., Deng, Y. & Sigurdsson, E. M. Mechanistic Studies of Antibody-Mediated Clearance of Tau Aggregates Using an ex vivo Brain Slice Model. Front Psychiatry 2, 59-65 (2011).
11. 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. 6, e26860 (2011).
12. Troquier, L. et al. Targeting phospho-Ser422 by active Tau immunotherapy in the THY-Tau22 mouse model: a suitable therapeutic approach. Curr. Alzheimer Res. 9, 397-405 (2012).
13. Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M. & Diamond, M. I. Trans-cellular Propagation of Tau Aggregation by Fibrillar Species. J. Biol Chem. 287, 19440-19451 (2012).
14. d'Abramo, C., Acker, C. M., Jimenez, H. T. & Davies, P. Tau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity. PLoS ONE 8, e62402 (2013).
15. Theunis, C. et al. Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau P301L mice that model tauopathy. PLoS. One. 8, e72301 (2013).
16. Yanamandra, K. et al. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80, 402-414 (2013).
17. Gu, J., Congdon, E. E. & Sigurdsson, E. M. Two novel Tau antibodies targeting the 396/404 region are primarily taken up by neurons and reduce Tau protein pathology. J. Biol Chem. 288, 33081-33095 (2013).
18. Congdon, E. E., Gu, J., Sait, H. B. & Sigurdsson, E. M. Antibody Uptake into Neurons Occurs Primarily via Clathrin-dependent Fcgamma Receptor Endocytosis and Is a Prerequisite for Acute Tau Protein Clearance. J. Biol Chem. 288, 35452-35465 (2013).
19. Castillo-Carranza, D. L. et al. Specific targeting of tau oligomers in htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds. J. Alzheimers. Dis. 40, S97-S111 (2014).
20. Castillo-Carranza, D. L. et al. Passive Immunization with Tau Oligomer Monoclonal Antibody Reverses Tauopathy Phenotypes without Affecting Hyperphosphorylated Neurofibrillary Tangles. J. Neurosci. 34, 4260-4272 (2014).
21. Collin, L. et al. Neuronal uptake of tau/pS422 antibody and reduced progression of tau pathology in a mouse model of Alzheimer's disease. Brain 137, 2834-2846 (2014).
22. Ittner, A. et al. Tau-targeting passive immunization modulates aspects of pathology in tau transgenic mice. J. Neurochem. 132, 135-145 (2015).
23. 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. Alzheimers. Res. Ther. 6, 44 (2014).
24. Selenica, M. L. et al. Epitope analysis following active immunization with tau proteins reveals immunogens implicated in tau pathogenesis. J. Neuroinflammation. 11, 152 (2014).
25. Ando, K. et al. Vaccination with Sarkosyl insoluble PHF-tau decrease neurofibrillary tangles formation in aged tau transgenic mouse model: a pilot study. J. Alzheimers. Dis. 40(Suppl 1), S135-S145 (2014).
26. Castillo-Carranza, D. L. et al. Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds. J. Alzheimers. Dis. 40(Suppl 1), S97-S111 (2014).
27. Umeda, T. et al. Passive immunotherapy of tauopathy targeting pSer413-tau: a pilot study in mice. Ann. Clin. Transl. Neurol. 2, 241-255 (2015).
28. Sankaranarayanan, S. et al. Passive immunization with phospho-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models. PLoS. One. 10, e0125614 (2015).
29. Yanamandra, K. et al. Anti-tau antibody reduces insoluble tau and decreases brain atrophy. Ann. Clin. Transl. Neurol. 2, 278-288 (2015).
30. d'Abramo, C., Acker, C. M., Jimenez, H. & Davies, P. Passive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies. PLoS. One. 10, e0135774 (2015).
31. Luo, W. et al. Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody. Sci. Rep. 5, 11161 (2015).
32. Funk, K. E., Mirbaha, H., Jiang, H., Holtzman, D. M. & Diamond, M. I. Distinct Therapeutic Mechanisms of Tau Antibodies: Promoting Microglial Clearance Versus Blocking Neuronal Uptake. J. Biol. Chem. 290, 21652-21662 (2015).
33. Schroeder, S. K., Joly-Amado, A., Gordon, M. N. & Morgan, D. Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer's Disease and Other Tauopathies. J. Neuroimmune Pharmacol. 11, 9-25 (2016).
34. Congdon, E. E. et al. Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy. Mol. Neurodegener. 11, 62-85 (2016).
35. Liu, W. et al. Vectored Intracerebral Immunization with the Anti-Tau Monoclonal Antibody PHF1 Markedly Reduces Tau Pathology in Mutant Tau Transgenic Mice. J. Neurosci. 36, 12425-12435 (2016).
36. Pedersen, J. T. & Sigurdsson, E. M. Tau immunotherapy for Alzheimer's disease. Trends Mol. Med. 21, 394-402 (2015).
37. Castillo-Carranza, D. L. et al. Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model. J. Neurosci. 35, 4857-4868 (2015).
38. Mably, A. J. et al. Tau immunization: a cautionary tale? Neurobiol. Aging 36, 1316-1332 (2015).
39. Rosenmann, H. et al. Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein. Archives of Neurology 63, 1459-1467 (2006).
40. Rozenstein-Tsalkovich, L. et al. Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation. Exp. Neurol. 248, 451-456 (2013).
41. Oddo, S. et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: Intracellular A? and synaptic dysfunction. Neuron 39, 409-421 (2003).
42. Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H. & LaFerla, F. M. A? immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 43, 321-332 (2004).
43. Walls, K. C. et al. p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice. Neurosci. Lett. 575, 96-100 (2014).
44. Dai, C. L., Tung, Y. C., Liu, F., Gong, C. X. & Iqbal, K. Tau passive immunization inhibits not only tau but also A? pathology. Alzheimers. Res. Ther. 9, 1 (2017).
45. 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 849, 529-540 (2012).
46. Davenport, J. W., Hagquist, W. W. & Rankin, G. R. Symmetrical Maze-An Automated Closed-Field Test Series for Rats. Behavior Research Methods & Instrumentation 2, 112-118 (1970).
47. Hebb, D. O. & Williams, K. A. A method of rating animal intelligence. J. Gen. Psychol. 34, 59-65 (1946).
48. Rabinovitch, M. S. & Rosvold, H. E. A closed-field intelligence test for rats. Can. J psychol. 5, 122-128 (1951).
49. Sigurdsson, E. M., Scholtzova, H., Mehta, P. D., Frangione, B. & Wisniewski, T. Immunization with a non-toxic/non-fibrillar amyloid-? homologous peptide reduces Alzheimer's disease associated pathology in transgenic mice. Am. J. Pathol. 159, 439-447 (2001).
50. Sigurdsson, E. M. et al. An attenuated immune response is sufficient to enhance cognition in an Alzheimer's disease mouse model immunized with amyloid-? derivatives. J Neurosci. 24, 6277-6282 (2004).
51. Sigurdsson, E. M., Lorens, S. A., Hejna, M. J., Dong, X. W. & Lee, J. M. Local and distant histopathological effects of unilateral amyloid-? 25-35 injections into the amygdala of young F344 rats. Neurobiol. Aging 17, 893-901 (1996).
52. Rajamohamedsait, H. B. & Sigurdsson, E. M. Histological Staining of Amyloid and Pre-amyloid Peptides and Proteins in Mouse Tissue. Methods Mol Biol 849, 411-424 (2012).
53. Sigurdsson, E. M., Lee, J. M., Dong, X. W., Hejna, M. J. & Lorens, S. A. Bilateral injections of amyloid-? 25-35 into the amygdala of young Fischer rats: Behavioral, neurochemical, and time dependent histopathological effects. Neurobiology of Aging 18, 591-608 (1997).
54. Asuni, A. A. et al. Vaccination of Alzheimer's model mice with A? derivative in alum adjuvant reduces A? burden without microhemorrhages. Eur. J Neurosci. 24, 2530-2542 (2006).
55. Billings, L. M., Oddo, S., Green, K. N., McGaugh, J. L. & LaFerla, F. M. Intraneuronal A? causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 45, 675-688 (2005).
56. Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A. & Van Eldik, L. J. Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet. 5, 88 (2014).
57. Krishnaswamy, S. et al. Antibody-derived in vivo imaging of tau pathology. J. Neurosci. 34, 16835-16850 (2014).