Advertisement

Amyloid-β pathology enhances pathological fibrillary tau seeding induced by Alzheimer PHF in vivo

  • Cristina Vergara
  • Sarah Houben
  • Valérie Suain
  • Zehra Yilmaz
  • Robert De Decker
  • Virginie Vanden Dries
  • Alain Boom
  • Salwa Mansour
  • Karelle Leroy
  • Kunie Ando
  • Jean-Pierre BrionEmail author
Original Paper

Abstract

Neuropathological analysis in Alzheimer’s disease (AD) and experimental evidence in transgenic models overexpressing frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) mutant tau suggest that amyloid-β pathology enhances the development of tau pathology. In this work, we analyzed this interaction independently of the overexpression of an FTDP-17 mutant tau, by analyzing tau pathology in wild-type (WT), 5xFAD, APP−/− and tau−/− mice after stereotaxic injection in the somatosensory cortex of short-length native human AD-PHF. Gallyas and phosphotau-positive tau inclusions developed in WT, 5xFAD, and APP−/− but not in tau−/− mice. Ultrastructural analysis demonstrated their intracellular localization and that they were composed of straight filaments. These seeded tau inclusions were composed only of endogenous murine tau exhibiting a tau antigenic profile similar to tau aggregates in AD. Insoluble tau level was higher and ipsilateral anteroposterior and contralateral cortical spreading of tau inclusions was more important in AD-PHF-injected 5xFAD mice than in WT mice. The formation of large plaque-associated dystrophic neurites positive for oligomeric and phosphotau was observed in 5xFAD mice injected with AD-PHF but never in control-injected or in non-injected 5xFAD mice. An increased level of the p25 activator of CDK5 kinase was found in AD-PHF-injected 5xFAD mice. These data demonstrate in vivo that the presence of Aβ pathology enhances experimentally induced tau seeding of endogenous, wild-type tau expressed at physiological level, and demonstrate the fibrillar nature of heterotopically seeded endogenous tau. These observations further support the hypothesis that Aβ enhances tau pathology development in AD through increased pathological tau spreading.

Keywords

Paired helical filaments Neurofibrillary tangles Aβ Prion-like tau propagation Tau seeding Alzheimer’s disease 

Notes

Acknowledgements

This study was supported by grants from the Belgian Fonds de la Recherche Scientifique Médicale (T.0023.15, T.0027.19), the Fund Aline (King Baudouin Foundation), the Foundation for Alzheimer Research (FRA/SAO) and the Génicot Fund. 3-D Deep imaging was performed in the Neurophysiology Laboratory and Light Microscopy Facility, Faculty of Medicine, Université Libre de Bruxelles. We thank Dr. Jean-Nöel Octave for the 3H5 antibody, Dr. Peter Davies for PHF1, Alz50 and MC1 antibodies, and Dr. Rakez Kayed for tau T22 antibody.

Supplementary material

401_2018_1953_MOESM1_ESM.mp4 (27.6 mb)
Supplementary material 1 (MP4 28263 kb)
401_2018_1953_MOESM2_ESM.pdf (5.9 mb)
Supplementary material 2 (PDF 6026 kb)

References

  1. 1.
    Ando K, Laborde Q, Brion JP, Duyckaerts C (2018) 3D imaging in the postmortem human brain with CLARITY and CUBIC. Handb Clin Neurol 150:303–317.  https://doi.org/10.1016/B978-0-444-63639-3.00021-9 CrossRefPubMedGoogle Scholar
  2. 2.
    Ando K, Tomimura K, Sazdovitch V, Suain V, Yilmaz Z, Authelet M et al (2016) Level of PICALM, a key component of clathrin-mediated endocytosis, is correlated with levels of phosphotau and autophagy-related proteins and is associated with tau inclusions in AD, PSP and Pick disease. Neurobiol Dis 94:32–43.  https://doi.org/10.1016/j.nbd.2016.05.017 CrossRefPubMedGoogle Scholar
  3. 3.
    Audouard E, Houben S, Masaracchia C, Yilmaz Z, Suain V, Authelet M et al (2016) High-molecular-weight paired helical filaments from Alzheimer brain induces seeding of wild-type mouse tau into an argyrophilic 4R tau pathology in vivo. Am J Pathol 186:2709–2722.  https://doi.org/10.1016/j.ajpath.2016.06.008 CrossRefPubMedGoogle Scholar
  4. 4.
    Bennett RE, DeVos SL, Dujardin S, Corjuc B, Gor R, Gonzalez J et al (2017) Enhanced tau aggregation in the presence of amyloid β. Am J Pathol 187:1601–1612.  https://doi.org/10.1016/j.ajpath.2017.03.011 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bolmont T, Clavaguera F, Meyer-Luehmann M, Herzig MC, Radde R, Staufenbiel M et al (2007) Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP × Tau transgenic mice. Am J Pathol 171:2012–2020.  https://doi.org/10.2353/ajpath.2007.070403 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Boutajangout A, Leroy K, Touchet N, Authelet M, Blanchard V, Tremp G et al (2002) Increased tau phosphorylation but absence of formation of neurofibrillary tangles in mice double transgenic for human tau and Alzheimer mutant (M146L) presenilin-1. Neurosci Lett 318:29–33CrossRefGoogle Scholar
  7. 7.
    Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefGoogle Scholar
  8. 8.
    Brion JP, Hanger DP, Couck AM, Anderton BH (1991) A68 proteins in Alzheimer’s disease are composed of several tau isoforms in a phosphorylated state which affects their electrophoretic mobilities. Biochem J 279(Pt 3):831–836CrossRefGoogle Scholar
  9. 9.
    Clavaguera F, Akatsu H, Fraser G, Crowther RA, Frank S, Hench J et al (2013) Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci USA 110:9535–9540.  https://doi.org/10.1073/pnas.1301175110 CrossRefPubMedGoogle Scholar
  10. 10.
    Clavaguera F, Hench J, Goedert M, Tolnay M (2015) Invited review: prion-like transmission and spreading of tau pathology. Neuropathol Appl Neurobiol 41:47–58.  https://doi.org/10.1111/nan.12197 CrossRefPubMedGoogle Scholar
  11. 11.
    Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I et al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–766.  https://doi.org/10.1007/s00401-014-1349-0 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Crowther RA (1991) Straight and paired helical filaments in Alzheimer disease have a common structural unit. Proc Natl Acad Sci USA 88:2288–2292CrossRefGoogle Scholar
  13. 13.
    Crowther RA, Goedert M (2000) Abnormal tau-containing filaments in neurodegenerative diseases. J Struct Biol 130:271–279.  https://doi.org/10.1006/jsbi.2000.4270 CrossRefPubMedGoogle Scholar
  14. 14.
    Cruz JC, Tseng HC, Goldman JA, Shih H, Tsai LH (2003) Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40:471–483CrossRefGoogle Scholar
  15. 15.
    Custo Greig LF, Woodworth MB, Galazo MJ, Padmanabhan H, Macklis JD (2013) Molecular logic of neocortical projection neuron specification, development and diversity. Nat Rev Neurosci 14:755–769.  https://doi.org/10.1038/nrn3586 CrossRefGoogle Scholar
  16. 16.
    Dickson DW, Rademakers R, Hutton ML (2007) Progressive supranuclear palsy: pathology and genetics. Brain Pathol 17:74–82.  https://doi.org/10.1111/j.1750-3639.2007.00054.x CrossRefPubMedGoogle Scholar
  17. 17.
    Duyckaerts C, Braak H, Brion JP, Buee L, Del Tredici K, Goedert M et al (2015) PART is part of Alzheimer disease. Acta Neuropathol 129:749–756.  https://doi.org/10.1007/s00401-015-1390-7 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118:5–36.  https://doi.org/10.1007/s00401-009-0532-1 CrossRefPubMedGoogle Scholar
  19. 19.
    Falcon B, Cavallini A, Angers R, Glover S, Murray TK, Barnham L et al (2015) Conformation determines the seeding potencies of native and recombinant Tau aggregates. J Biol Chem 290:1049–1065.  https://doi.org/10.1074/jbc.M114.589309 CrossRefPubMedGoogle Scholar
  20. 20.
    Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ et al (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547:185–190.  https://doi.org/10.1038/nature23002 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT et al (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640.  https://doi.org/10.1126/science.1082324 CrossRefPubMedGoogle Scholar
  22. 22.
    Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA (1996) Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 383:550–553.  https://doi.org/10.1038/383550a0 CrossRefPubMedGoogle Scholar
  23. 23.
    Gotz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301 l tau transgenic mice induced by Abeta 42 fibrils. Science 293:1491–1495.  https://doi.org/10.1126/science.1062097 CrossRefPubMedGoogle Scholar
  24. 24.
    Guo JL, Narasimhan S, Changolkar L, He Z, Stieber A, Zhang B et al (2016) Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice. J Exp Med 213:2635–2654.  https://doi.org/10.1084/jem.20160833 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Guo JP, Arai T, Miklossy J, McGeer PL (2006) Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer’s disease. Proc Natl Acad Sci USA 103:1953–1958.  https://doi.org/10.1073/pnas.0509386103 CrossRefPubMedGoogle Scholar
  26. 26.
    He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L et al (2018) Amyloid-beta plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29–38.  https://doi.org/10.1038/nm.4443 CrossRefPubMedGoogle Scholar
  27. 27.
    Héraud C, Goufak D, Ando K, Leroy K, Suain V, Yilmaz Z et al (2014) Increased misfolding and truncation of tau in APP/PS1/tau transgenic mice compared to mutant tau mice. Neurobiol Dis 62:100–112.  https://doi.org/10.1016/j.nbd.2013.09.010 CrossRefPubMedGoogle Scholar
  28. 28.
    Hurtado DE, Molina-Porcel L, Iba M, Aboagye AK, Paul SM, Trojanowski JQ et al (2010) A{beta} accelerates the spatiotemporal progression of tau pathology and augments tau amyloidosis in an Alzheimer mouse model. Am J Pathol 177:1977–1988.  https://doi.org/10.2353/ajpath.2010.100346 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Jackson SJ, Kerridge C, Cooper J, Cavallini A, Falcon B, Cella CV et al (2016) Short fibrils constitute the major species of seed-competent tau in the brains of mice transgenic for human P301S tau. J Neurosci 36:762–772.  https://doi.org/10.1523/JNEUROSCI.3542-15.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Janke C, Beck M, Stahl T, Holzer M, Brauer K, Bigl V et al (1999) Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders. Brain Res Mol Brain Res 68:119–128CrossRefGoogle Scholar
  31. 31.
    Kaufman SK, Sanders DW, Thomas TL, Ruchinskas AJ, Vaquer-Alicea J, Sharma AM et al (2016) Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. Neuron 92:796–812.  https://doi.org/10.1016/j.neuron.2016.09.055 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kidd M (1963) Paired helical filaments in electron microscopy of Alzheimer’s disease. Nature 197:192–193.  https://doi.org/10.1038/197192b0 CrossRefPubMedGoogle Scholar
  33. 33.
    Lasagna-Reeves CA, Castillo-Carranza DL, Guerrero-Muoz MJ, Jackson GR, Kayed R (2010) Preparation and characterization of neurotoxic tau oligomers. Biochemistry 49:10039–10041.  https://doi.org/10.1021/bi1016233 CrossRefPubMedGoogle Scholar
  34. 34.
    Leroy K, Ando K, Heraud C, Yilmaz Z, Authelet M, Boeynaems JM et al (2010) Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology. J Alzheimers Dis 19:705–719.  https://doi.org/10.3233/JAD-2010-1276 CrossRefPubMedGoogle Scholar
  35. 35.
    Leroy K, Ando K, Laporte V, Dedecker R, Suain V, Authelet M et al (2012) Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice. Am J Pathol 181:1928–1940.  https://doi.org/10.1016/j.ajpath.2012.08.012 CrossRefPubMedGoogle Scholar
  36. 36.
    Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G et al (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293:1487–1491.  https://doi.org/10.1126/science.1058189 CrossRefPubMedGoogle Scholar
  37. 37.
    Masliah E, Sisk A, Mallory M, Games D (2001) Neurofibrillary pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. J Neuropathol Exp Neurol 60:357–368CrossRefGoogle Scholar
  38. 38.
    Miller Y, Ma B, Nussinov R (2011) Synergistic interactions between repeats in tau protein and Abeta amyloids may be responsible for accelerated aggregation via polymorphic states. Biochemistry 50:5172–5181.  https://doi.org/10.1021/bi200400u CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Morel M, Authelet M, Dedecker R, Brion JP (2010) Glycogen synthase kinase-3beta and the p25 activator of cyclin dependent kinase 5 increase pausing of mitochondria in neurons. Neuroscience 167:1044–1056.  https://doi.org/10.1016/j.neuroscience.2010.02.077 CrossRefPubMedGoogle Scholar
  40. 40.
    Mudher A, Colin M, Dujardin S, Medina M, Dewachter I, Naini SMA et al (2017) What is the evidence that tau pathology spreads through prion-like propagation? Acta Neuropathol Commun 5:99.  https://doi.org/10.1186/s40478-017-0488-7 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Narasimhan S, Guo JL, Changolkar L, Stieber A, McBride JD, Silva LV et al (2017) Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain. J Neurosci 37:11406–11423.  https://doi.org/10.1523/JNEUROSCI.1230-17.2017 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ et al (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362–381.  https://doi.org/10.1097/NEN.0b013e31825018f7 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J et al (2003) Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 38:555–565CrossRefGoogle Scholar
  44. 44.
    Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J et al (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26:10129–10140CrossRefGoogle Scholar
  45. 45.
    Otth C, Concha II, Arendt T, Stieler J, Schliebs R, Gonzalez-Billault C et al (2002) AbetaPP induces cdk5-dependent tau hyperphosphorylation in transgenic mice Tg2576. J Alzheimers Dis 4:417–430CrossRefGoogle Scholar
  46. 46.
    Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402:615–622.  https://doi.org/10.1038/45159 CrossRefPubMedGoogle Scholar
  47. 47.
    Perez M, Ribe E, Rubio A, Lim F, Moran MA, Ramos PG et al (2005) Characterization of a double (amyloid precursor protein-tau) transgenic: tau phosphorylation and aggregation. Neuroscience 130:339–347.  https://doi.org/10.1016/j.neuroscience.2004.09.029 CrossRefPubMedGoogle Scholar
  48. 48.
    Pooler AM, Polydoro M, Maury EA, Nicholls SB, Reddy SM, Wegmann S et al (2015) Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease. Acta Neuropathol Commun 3:14.  https://doi.org/10.1186/s40478-015-0199-x CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Sanders DW, Kaufman SK, Holmes BB, Diamond MI (2016) Prions and protein assemblies that convey biological information in health and disease. Neuron 89:433–448.  https://doi.org/10.1016/j.neuron.2016.01.026 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Seino Y, Kawarabayashi T, Wakasaya Y, Watanabe M, Takamura A, Yamamoto-Watanabe Y et al (2010) Amyloid beta accelerates phosphorylation of tau and neurofibrillary tangle formation in an amyloid precursor protein and tau double-transgenic mouse model. J Neurosci Res 88:3547–3554.  https://doi.org/10.1002/jnr.22516 CrossRefPubMedGoogle Scholar
  51. 51.
    Stancu IC, Ris L, Vasconcelos B, Marinangeli C, Goeminne L, Laporte V et al (2014) Tauopathy contributes to synaptic and cognitive deficits in a murine model for Alzheimer’s disease. FASEB J 28:2620–2631.  https://doi.org/10.1096/fj.13-246702 CrossRefPubMedGoogle Scholar
  52. 52.
    Susaki EA, Tainaka K, Perrin D, Kishino F, Tawara T, Watanabe TM et al (2014) Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157:726–739.  https://doi.org/10.1016/j.cell.2014.03.042 CrossRefPubMedGoogle Scholar
  53. 53.
    Taniguchi-Watanabe S, Arai T, Kametani F, Nonaka T, Masuda-Suzukake M, Tarutani A et al (2016) Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau. Acta Neuropathol 131:267–280.  https://doi.org/10.1007/s00401-015-1503-3 CrossRefPubMedGoogle Scholar
  54. 54.
    Terry RD (1963) The fine structure of neurofibrillary tangles in Alzheimer’s disease. J Neuropathol Exp Neurol 22:629–642CrossRefGoogle Scholar
  55. 55.
    Terwel D, Muyllaert D, Dewachter I, Borghgraef P, Croes S, Devijver H et al (2008) Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol 172:786–798.  https://doi.org/10.2353/ajpath.2008.070904 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Tucker KL, Meyer M, Barde YA (2001) Neurotrophins are required for nerve growth during development. Nat Neurosci 4:29–37CrossRefGoogle Scholar
  57. 57.
    Vanden Dries V, Stygelbout V, Pierrot N, Yilmaz Z, Suain V, De Decker R et al (2017) Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model. Neurobiol Aging 55:202–212.  https://doi.org/10.1016/j.neurobiolaging.2017.03.031 CrossRefPubMedGoogle Scholar
  58. 58.
    Vasconcelos B, Stancu IC, Buist A, Bird M, Wang P, Vanoosthuyse A et al (2016) Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo. Acta Neuropathol 131:549–569.  https://doi.org/10.1007/s00401-015-1525-x CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW et al (1995) beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81:525–531CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Cristina Vergara
    • 1
  • Sarah Houben
    • 1
  • Valérie Suain
    • 1
  • Zehra Yilmaz
    • 1
  • Robert De Decker
    • 1
  • Virginie Vanden Dries
    • 1
  • Alain Boom
    • 1
  • Salwa Mansour
    • 1
  • Karelle Leroy
    • 1
  • Kunie Ando
    • 1
  • Jean-Pierre Brion
    • 1
    Email author return OK on get
  1. 1.Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Faculty of MedicineUniversité Libre de BruxellesBrusselsBelgium

Personalised recommendations