Advertisement

Necrosome complex detected in granulovacuolar degeneration is associated with neuronal loss in Alzheimer’s disease

  • Marta J. Koper
  • Evelien Van Schoor
  • Simona Ospitalieri
  • Rik Vandenberghe
  • Mathieu Vandenbulcke
  • Christine A. F. von Arnim
  • Thomas Tousseyn
  • Sriram Balusu
  • Bart De StrooperEmail author
  • Dietmar Rudolf ThalEmail author
Original Paper

Abstract

Alzheimer’s disease (AD) is characterized by a specific pattern of neuropathological changes, including extracellular amyloid β (Aβ) deposits, intracellular neurofibrillary tangles (NFTs), granulovacuolar degeneration (GVD) representing cytoplasmic vacuolar lesions, synapse dysfunction and neuronal loss. Necroptosis, a programmed form of necrosis characterized by the assembly of the necrosome complex composed of phosphorylated proteins, i.e. receptor-interacting serine/threonine-protein kinase 1 and 3 (pRIPK1 and pRIPK3) and mixed lineage kinase domain-like protein (pMLKL), has recently been shown to be involved in AD. However, it is not yet clear whether necrosome assembly takes place in brain regions showing AD-related neuronal loss and whether it is associated with AD-related neuropathological changes. Here, we analyzed brains of AD, pathologically defined preclinical AD (p-preAD) and non-AD control cases to determine the neuropathological characteristics and distribution pattern of the necrosome components. We demonstrated that all three activated necrosome components can be detected in GVD lesions (GVDn+, i.e. GVD with activated necrosome) in neurons, that they colocalize with classical GVD markers, such as pTDP-43 and CK1δ, and similarly to these markers detect GVD lesions. GVDn + neurons inversely correlated with neuronal density in the early affected CA1 region of the hippocampus and in the late affected frontal cortex layer III. Additionally, AD-related GVD lesions were associated with AD-defining parameters, showing the strongest correlation and partial colocalization with NFT pathology. Therefore, we conclude that the presence of the necrosome in GVD plays a role in AD, possibly by representing an AD-specific form of necroptosis-related neuron death. Hence, necroptosis-related neuron loss could be an interesting therapeutic target for treating AD.

Keywords

Necroptosis Granulovacuolar degeneration Alzheimer’s disease Neuronal loss Necrosome pMLKL 

Notes

Acknowledgements

The authors gratefully acknowledge the assistance of Mrs. Alicja Ronisz. They also thank Mathias De Decker (Laboratory for Neurobiology, VIB-KU Leuven, Belgium) for providing SH-SY5Y cells. Also, we thank the VIB Imaging Core Facility in Leuven for expert assistance and overall technical support in super-resolution imaging of cleared tissue using spinning disk confocal microscopy. The study was supported by: Fonds Wetenschappelijk Onderzoek (FWO) G0F8516N, 1S46219N, (DRT, RV); C1-internal funds from KU Leuven C14-17-107 (DRT); Vlaamse Impulsfinanciering voor Netwerken voor Dementie-onderzoek (IWT 135043) (RV, BDS, DRT) and a Methusalem grant of the Flemish Government and the KU Leuven to BDS. EVS is funded by an SB PhD Fellowship of FWO-Vlaanderen (1S46219N). SB received a post-doc fellowship from FWO-Vlaaderen (12P5919N).

Compliance with ethical standards

Conflict of interest

DRT received consultant honorary from GE Healthcare (UK) and Covance Laboratories (UK), speaker honorary from Novartis Pharma AG (Switzerland), travel reimbursement from GE Healthcare (UK) and UCB (Belgium) and collaborated with Novartis Pharma AG (Switzerland), Probiodrug (Germany), GE Healthcare (UK), and Janssen Pharmaceutical Companies (Belgium). BDS collaborated with Janssen Pharmaceutical companies (Belgium), Abbvie (USA) and received consulting fees from Eisai (Japan). None related to the work in this paper. RV’s institution has clinical trial agreements (RV as PI) with AbbVie, Genentech, Novartis, and Roche, material transfer agreements (RV as PI) with Avid a subsidiary of EliLilly, and consultancy agreements (RV as PI) with Prevail Therapeutics and Rodin Therapeutics. CAFvA received honoraria from serving on the scientific advisory board of Nutricia GmbH, Roche, Dr. Willmar Schwabe GmbH and Honkong University Research council and has received funding for travel and speaker honoraria from Nutricia GmbH, Lilly Deutschland GmbH, Desitin Arzneimittel GmbH, Biogen, Roche and Dr. Willmar Schwabe GmbH &Co. KG.

Supplementary material

401_2019_2103_MOESM1_ESM.pptx (65.9 mb)
Supplementary file1 (PPTX 67521 kb)
401_2019_2103_MOESM2_ESM.pdf (2.2 mb)
Supplementary file2 (PDF 2205 kb)
401_2019_2103_MOESM3_ESM.pdf (789 kb)
Supplementary file3 (PDF 788 kb)

References

  1. 1.
    Association A (2017) 2017 Alzheimer’s disease facts and figures. Alzheimer’s Dement 13:325–373.  https://doi.org/10.1016/j.jalz.2017.02.001 CrossRefGoogle Scholar
  2. 2.
    Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. Acta Neuropathol 37:111–118.  https://doi.org/10.1007/BF00692056 CrossRefPubMedGoogle Scholar
  3. 3.
    Ball MJ (1978) Topographic distribution of neurofibrillary tangles and granulovacuolar degeneration in hippocampal cortex of aging and demented patients. A quantitative study. Acta Neuropathol 42:73–80.  https://doi.org/10.1007/BF00690970 CrossRefPubMedGoogle Scholar
  4. 4.
    Balusu S, Brkic M, Libert C, Vandenbroucke RE (2016) The choroid plexus-cerebrospinal fluid interface in Alzheimer’s disease: more than just a barrier. Neural Regen Res 11:534.  https://doi.org/10.4103/1673-5374.180372 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated τ precedes the formation of neurofibrillary tangles in Alzheimer’s disease. Brain Res 477:90–99.  https://doi.org/10.1016/0006-8993(89)91396-6 CrossRefPubMedGoogle Scholar
  6. 6.
    Barnes J, Bartlett JW, van de Pol LA, Loy CT, Scahill RI, Frost C, Thompson P, Fox NC (2009) A meta-analysis of hippocampal atrophy rates in Alzheimer’s disease. Neurobiol Aging 30:1711–1723.  https://doi.org/10.1016/j.neurobiolaging.2008.01.010 CrossRefPubMedGoogle Scholar
  7. 7.
    Braak F, Braak H, Mandelkow E-M (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87:554–567.  https://doi.org/10.1007/BF00293315 CrossRefPubMedGoogle Scholar
  8. 8.
    Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112:389–404.  https://doi.org/10.1007/s00401-006-0127-z CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259.  https://doi.org/10.1007/BF00308809 CrossRefPubMedGoogle Scholar
  10. 10.
    Caccamo A, Branca C, Piras IS, Ferreira E, Huentelman MJ, Liang WS, Readhead B, Dudley JT, Spangenberg EE, Green KN, Belfiore R, Winslow W, Oddo S (2017) Necroptosis activation in Alzheimer’s disease. Nat Neurosci 20:1236–1246.  https://doi.org/10.1038/nn.4608 CrossRefPubMedGoogle Scholar
  11. 11.
    Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG (2014) Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 16:55–65.  https://doi.org/10.1038/ncb2883 CrossRefPubMedGoogle Scholar
  12. 12.
    Chen X, Li W, Ren J, Huang D, He W, Song Y, Yang C, Li W, Zheng X, Chen P, Han J (2013) Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res 24:105.  https://doi.org/10.1038/cr.2013.171 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cho Y, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK-M (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123.  https://doi.org/10.1016/j.cell.2009.05.037 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH (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
  15. 15.
    Dickson DW, Ksiezak-Reding H, Davies P, Yen S-H (1987) A monoclonal antibody that recognizes a phosphorylated epitope in Alzheimer neurofibrillary tangles, neurofilaments and tau proteins immunostains granulovacuolar degeneration. Acta Neuropathol 73:254–258.  https://doi.org/10.1007/BF00686619 CrossRefPubMedGoogle Scholar
  16. 16.
    Duyckaerts C, Delaère P, Hauw JJ (1992) Alzheimer’s disease and neuroanatomy: hypotheses and proposals. In: Boller F, Forette F, Khachatarian Z, Poncet M, Christen Y (eds) Heterogeneity of Alzheimer’s disease, Springer, Berlin, pp 144–155.  https://doi.org/10.1007/978-3-642-46776-9_15 Google Scholar
  17. 17.
    Eskelinen E-L, Saftig P (2009) Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta (BBA) Mol Cell Res 1793:664–673.  https://doi.org/10.1016/j.bbamcr.2008.07.014 CrossRefGoogle Scholar
  18. 18.
    Funk KE, Mrak RE, Kuret J (2011) Granulovacuolar degeneration (GVD) bodies of Alzheimer’s disease (AD) resemble late-stage autophagic organelles. Neuropathol Appl Neurobiol 37:295–306.  https://doi.org/10.1111/j.1365-2990.2010.01135.x CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ganz AB, Beker N, Hulsman M, Sikkes S, Bank NB, Scheltens P, Smit AB, Rozemuller AJM, Hoozemans JJM, Holstege H (2018) Neuropathology and cognitive performance in self-reported cognitively healthy centenarians. Acta Neuropathol Commun 6:64.  https://doi.org/10.1186/s40478-018-0558-5 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Giacobini E, Gold G (2013) Alzheimer disease therapy—moving from amyloid-β to tau. Nat Rev Neurol 9:677.  https://doi.org/10.1038/nrneurol.2013.223 CrossRefPubMedGoogle Scholar
  21. 21.
    Goodpaster T, Randolph-Habecker J (2014) A Flexible mouse-on-mouse immunohistochemical staining technique adaptable to biotin-free reagents, immunofluorescence, and multiple antibody staining. J Histochem Cytochem 62:197–204.  https://doi.org/10.1369/0022155413511620 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Grootjans S, Vanden Berghe T, Vandenabeele P (2017) Initiation and execution mechanisms of necroptosis: an overview. Cell Death Differ 24:1184–1195.  https://doi.org/10.1038/cdd.2017.65 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-α. Cell 137:1100–1111.  https://doi.org/10.1016/j.cell.2009.05.021 CrossRefPubMedGoogle Scholar
  24. 24.
    Hecht M, Kramer LM, von Arnim CAF, Otto M, Thal DR (2018) Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline. Acta Neuropathol 135:681-694.  https://doi.org/10.1007/s00401-018-1834-y CrossRefGoogle Scholar
  25. 25.
    Hildebrand JM, Tanzer MC, Lucet IS, Young SN, Spall SK, Sharma P, Pierotti C, Garnier J-M, Dobson RCJ, Webb AI (2014) Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci 111:15072–15077.  https://doi.org/10.1073/pnas.1408987111 CrossRefPubMedGoogle Scholar
  26. 26.
    Hirano A, Dembitzer HM, Kurland LT, Zimmerman HM (1968) The fine structure of some intraganglionic alterations: neurofibrillary tangles, granulovacuolar bodies and “rod-like” structures as seen in Guam amyotrophic lateral sclerosis and parkinsonism-dementia complex. J Neuropathol Exp Neurol 27:167–182.  https://doi.org/10.1097/00005072-196804000-00001 CrossRefPubMedGoogle Scholar
  27. 27.
    Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr SU, Culliford D, Perry VH (2009) Systemic inflammation and disease progression in Alzheimer disease. Neurology 73:768–774.  https://doi.org/10.1212/WNL.0b013e3181b6bb95 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Hoozemans JJM, van Haastert ES, Nijholt DAT, Rozemuller AJM, Eikelenboom P, Scheper W (2009) The unfolded protein response is activated in pretangle neurons in Alzheimer’s disease hippocampus. Am J Pathol 174:1241–1251.  https://doi.org/10.2353/ajpath.2009.080814 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 225:1168–1170.  https://doi.org/10.1126/science.6474172 CrossRefPubMedGoogle Scholar
  30. 30.
    Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E (2012) National institute on aging–Alzheimer’s association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimer’s Dement 8:1–13.  https://doi.org/10.1016/j.jalz.2011.10.007 CrossRefGoogle Scholar
  31. 31.
    Ito Y, Ofengeim D, Najafov A, Das S, Saberi S, Li Y, Hitomi J, Zhu H, Chen H, Mayo L (2016) RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science 353:603–608.  https://doi.org/10.1126/science.aaf6803 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Jing Z, Caltagarone J, Bowser R (2009) Altered subcellular distribution of c-Abl in Alzheimer’s disease. J Alzheimer’s Dis 17:409–422.  https://doi.org/10.3233/JAD-2009-1062 CrossRefGoogle Scholar
  33. 33.
    Kadokura A, Yamazaki T, Kakuda S, Makioka K, Lemere CA, Fujita Y, Takatama M, Okamoto K (2009) Phosphorylation-dependent TDP-43 antibody detects intraneuronal dot-like structures showing morphological characters of granulovacuolar degeneration. Neurosci Lett 463:87–92.  https://doi.org/10.1016/j.neulet.2009.06.024 CrossRefPubMedGoogle Scholar
  34. 34.
    Kannanayakal TJ, Tao H, Vandre DD, Kuret J (2006) Casein kinase-1 isoforms differentially associate with neurofibrillary and granulovacuolar degeneration lesions. Acta Neuropathol 111:413–421.  https://doi.org/10.1007/s00401-006-0049-9 CrossRefPubMedGoogle Scholar
  35. 35.
    Köhler C (2016) Granulovacuolar degeneration: a neurodegenerative change that accompanies tau pathology. Acta Neuropathol 132:339–359.  https://doi.org/10.1007/s00401-016-1562-0 CrossRefPubMedGoogle Scholar
  36. 36.
    Köhler C, Dinekov M, Götz J (2014) Granulovacuolar degeneration and unfolded protein response in mouse models of tauopathy and Aβ amyloidosis. Neurobiol Dis 71:169–179.  https://doi.org/10.1016/j.nbd.2014.07.006 CrossRefPubMedGoogle Scholar
  37. 37.
    Kumar S, Wirths O, Stüber K, Wunderlich P, Koch P, Theil S, Rezaei-Ghaleh N, Zweckstetter M, Bayer TA, Brüstle O, Thal DR, Walter J (2016) Phosphorylation of the amyloid β-peptide at Ser26 stabilizes oligomeric assembly and increases neurotoxicity. Acta Neuropathol 131:525–537.  https://doi.org/10.1007/s00401-016-1546-0 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lagalwar S, Guillozet-Bongaarts AL, Berry RW, Binder LI (2006) Formation of phospho-SAPK/JNK granules in the hippocampus is an early event in Alzheimer disease. J Neuropathol Exp Neurol 65:455–464.  https://doi.org/10.1097/01.jnen.0000229236.98124.d8 CrossRefPubMedGoogle Scholar
  39. 39.
    Leroy K, Boutajangout A, Authelet M, Woodgett JR, Anderton BH, Brion J-P (2002) The active form of glycogen synthase kinase-3β is associated with granulovacuolar degeneration in neurons in Alzheimer’s disease. Acta Neuropathol 103:91–99CrossRefGoogle Scholar
  40. 40.
    Lewis J, Dickson DW, Lin W-L, Chisholm L, Corral A, Jones G, Yen S-H, Sahara N, Skipper L, Yager D (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
  41. 41.
    Liu S, Liu H, Johnston A, Hanna-Addams S, Reynoso E, Xiang Y, Wang Z (2017) MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis. Proc Natl Acad Sci 114:E7450–E7459.  https://doi.org/10.1073/pnas.1707531114 CrossRefPubMedGoogle Scholar
  42. 42.
    Lockshin RA, Zakeri Z (2001) Programmed cell death and apoptosis: origins of the theory. Nat Rev Mol cell Biol 2:545.  https://doi.org/10.1038/35080097 CrossRefPubMedGoogle Scholar
  43. 43.
    Lund H, Gustafsson E, Svensson A, Nilsson M, Berg M, Sunnemark D, von Euler G (2014) MARK4 and MARK3 associate with early tau phosphorylation in Alzheimer’s disease granulovacuolar degeneration bodies. Acta Neuropathol Commun 2:22.  https://doi.org/10.1186/2051-5960-2-22 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD): Part II Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479.  https://doi.org/10.1212/WNL.41.4.479 CrossRefPubMedGoogle Scholar
  45. 45.
    Morris JC, Heyman A, Mohs RC, Hughes JP, Van Belle G, Fillenbaum G, Mellits ED, Clark C (1989) The consortium to establish a registry for Alzheimer’s disease (CERAD): I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology.  https://doi.org/10.1212/WNL.39.9.1159 CrossRefPubMedGoogle Scholar
  46. 46.
    Morsch R, Simon W, Coleman PD (1999) Neurons may live for decades with neurofibrillary tangles. J Neuropathol Exp Neurol 58:188–197.  https://doi.org/10.1097/00005072-199902000-00008 CrossRefPubMedGoogle Scholar
  47. 47.
    Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang J-G, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39:443–453.  https://doi.org/10.1016/j.immuni.2013.06.018 CrossRefPubMedGoogle Scholar
  48. 48.
    Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, Castellani RJ, Crain BJ, Davies P, Del TK (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
  49. 49.
    Nishikawa T, Takahashi T, Nakamori M, Hosomi N, Maruyama H, Miyazaki Y, Izumi Y, Matsumoto M (2016) The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments. Neuropathol Appl Neurobiol 42:639–653.  https://doi.org/10.1111/nan.12288 CrossRefPubMedGoogle Scholar
  50. 50.
    Ofengeim D, Ito Y, Najafov A, Zhang Y, Shan B, DeWitt JP, Ye J, Zhang X, Chang A, Vakifahmetoglu-Norberg H (2015) Activation of necroptosis in multiple sclerosis. Cell Rep 10:1836–1849.  https://doi.org/10.1016/j.celrep.2015.02.051 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Ofengeim D, Mazzitelli S, Ito Y, DeWitt JP, Mifflin L, Zou C, et al. (2017) RIPK1 mediates a disease-associated microglial response in Alzheimer's disease. Proc Natl Acad Sci U S A 114:E8788-E8797.  https://doi.org/10.1073/pnas.1714175114 CrossRefGoogle Scholar
  52. 52.
    Ohm TG, Müller H, Braak H, Bohl J (1995) Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer’s disease-related neurofibrillary changes. Neuroscience 64:209–217.  https://doi.org/10.1016/0306-4522(95)90397-P CrossRefPubMedGoogle Scholar
  53. 53.
    Okamoto K, Hirai S, Iizuka T, Yanagisawa T, Watanabe M (1991) Reexamination of granulovacuolar degeneration. Acta Neuropathol 82:340–345.  https://doi.org/10.1007/BF00296544 CrossRefPubMedGoogle Scholar
  54. 54.
    Pini L, Pievani M, Bocchetta M, Altomare D, Bosco P, Cavedo E, Galluzzi S, Marizzoni M, Frisoni GB (2016) Brain atrophy in Alzheimer’s disease and aging. Ageing Res Rev 30:25–48.  https://doi.org/10.1016/j.arr.2016.01.002 CrossRefPubMedGoogle Scholar
  55. 55.
    Re DB, Le Verche V, Yu C, Amoroso MW, Politi KA, Phani S, Ikiz B, Hoffmann L, Koolen M, Nagata T (2014) Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron 81:1001–1008.  https://doi.org/10.1016/j.neuron.2014.01.011 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Rijal Upadhaya A, Kosterin I, Kumar S, Von Arnim CAF, Yamaguchi H, Fändrich M, Walter J, Thal DR (2014) Biochemical stages of amyloid-β peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically preclinical Alzheimer’s disease. Brain 137:887–903.  https://doi.org/10.1093/brain/awt362 CrossRefPubMedGoogle Scholar
  57. 57.
    Riku Y, Duyckaerts C, Boluda S, Plu I, Le Ber I, Millecamps S, et al. (2019) Increased prevalence of granulovacuolar degeneration in C9orf72 mutation. Acta Neuropathol 138:783-793.  https://doi.org/10.1007/s00401-019-02028-6 CrossRefGoogle Scholar
  58. 58.
    Ros U, Peña-Blanco A, Hänggi K, Kunzendorf U, Krautwald S, Wong WWL, García-Sáez AJ (2017) Necroptosis execution is mediated by plasma membrane nanopores independent of calcium. Cell Rep 19:175–187.  https://doi.org/10.1016/j.celrep.2017.03.024 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Rossi S, Motta C, Studer V, Barbieri F, Buttari F, Bergami A, Sancesario G, Bernardini S, De Angelis G, Martino G (2014) Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration. Mult Scler J 20:304–312.  https://doi.org/10.1177/1352458513498128 CrossRefGoogle Scholar
  60. 60.
    Sassin I, Schultz C, Thal DR, Rüb U, Arai K, Braak E, Braak H (2000) Evolution of Alzheimer’s disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol 100:259–269.  https://doi.org/10.1007/s004019900178 CrossRefPubMedGoogle Scholar
  61. 61.
    Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27:1372–1384.  https://doi.org/10.1016/j.neurobiolaging.2005.09.012 CrossRefPubMedGoogle Scholar
  62. 62.
    Schwab C, DeMaggio AJ, Ghoshal N, Binder LI, Kuret J, McGeer PL (2000) Casein kinase 1 delta is associated with pathological accumulation of tau in several neurodegenerative diseases. Neurobiol Aging 21:503–510.  https://doi.org/10.1016/S0197-4580(00)00110-X CrossRefPubMedGoogle Scholar
  63. 63.
    Selznick LA, Holtzman DM, Han BH, Gökden M, Srinivasan AN, Johnson EM Jr, Roth KA (1999) In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease. J Neuropathol Exp Neurol 58:1020–1026.  https://doi.org/10.1097/00005072-199909000-00012 CrossRefPubMedGoogle Scholar
  64. 64.
    Simchowicz T (1911) Histopathologische Studien über die senile Demenz. In: F. Nissl, and A. Alzheimer (eds) Histologie und histopathologische Arbeiten über die Großhirnrinde, Fischer, Jena, pp 267–444Google Scholar
  65. 65.
    Stadelmann C, Deckwerth TL, Srinivasan A, Bancher C, Brück W, Jellinger K, Lassmann H (1999) Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer’s disease: evidence for apoptotic cell death. Am J Pathol 155:1459–1466.  https://doi.org/10.1016/S0002-9440(10)65460-0 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Stadelmann C, Lassmann H (2000) Detection of apoptosis in tissue sections. Cell Tissue Res 301:19–31.  https://doi.org/10.1007/s004410000203 CrossRefPubMedGoogle Scholar
  67. 67.
    Su JH, Kesslak PJ, Head E, Cotman CW (2002) Caspase-cleaved amyloid precursor protein and activated caspase-3 are co-localized in the granules of granulovacuolar degeneration in Alzheimer’s disease and Down’s syndrome brain. Acta Neuropathol 104:1–6.  https://doi.org/10.1007/s00401-002-0548-2 CrossRefPubMedGoogle Scholar
  68. 68.
    Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148:213–227.  https://doi.org/10.1016/j.cell.2011.11.031 CrossRefPubMedGoogle Scholar
  69. 69.
    Susaki EA, Tainaka K, Perrin D, Yukinaga H, Kuno A, Ueda HR (2015) Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging. Nat Protoc 10:1709.  https://doi.org/10.1038/nprot.2015.085 CrossRefPubMedGoogle Scholar
  70. 70.
    Terry RD, DeTeresa R, Hansen LA (1987) Neocortical cell counts in normal human adult aging. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc 21:530–539.  https://doi.org/10.1002/ana.410210603 CrossRefGoogle Scholar
  71. 71.
    Thal DR, Holzer M, Rüb U, Waldmann G, Günzel S, Zedlick D, Schober R (2000) Alzheimer-related τ-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol 163:98–110.  https://doi.org/10.1006/exnr.2000.7380 CrossRefPubMedGoogle Scholar
  72. 72.
    Thal DR, Rüb U, Orantes M, Braak H (2002) Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800.  https://doi.org/10.1212/WNL.58.12.1791 CrossRefPubMedGoogle Scholar
  73. 73.
    Thal DR, Rüb U, Schultz C, Sassin I, Ghebremedhin E, Del Tredici K, Braak E, Braak H (2000) Sequence of Aβ-protein deposition in the human medial temporal lobe. J Neuropathol Exp Neurol 59:733–748.  https://doi.org/10.1093/jnen/59.8.733 CrossRefPubMedGoogle Scholar
  74. 74.
    Thal DR, Del Tredici K, Ludolph AC, Hoozemans JJM, Rozemuller AJ, Braak H, Knippschild U (2011) Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response. Acta Neuropathol 122:577–589.  https://doi.org/10.1007/s00401-011-0871-6 CrossRefPubMedGoogle Scholar
  75. 75.
    Tomlinson BE, Kitchener D (1972) Granulovacuolar degeneration of hippocampal pyramidal cells. J Pathol 106:165–185.  https://doi.org/10.1002/path.1711060305 CrossRefPubMedGoogle Scholar
  76. 76.
    Virard F, Cousty S, Cambus J-P, Valentin A, Kémoun P, Clément F (2015) Cold atmospheric plasma induces a predominantly necrotic cell death via the microenvironment. PLoS ONE 10:e0133120.  https://doi.org/10.1371/journal.pone.0133120 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Wang Y, Martinez-Vicente M, Krüger U, Kaushik S, Wong E, Mandelkow E-M, Cuervo AM, Mandelkow E (2009) Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum Mol Genet 18:4153–4170.  https://doi.org/10.1093/hmg/ddp367 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Wegner KW, Saleh D, Degterev A (2017) Complex pathologic roles of RIPK1 and RIPK3: moving beyond necroptosis. Trends Pharmacol Sci 38:202–225.  https://doi.org/10.1016/j.tips.2016.12.005 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    West MJ, Coleman PD, Flood DG, Troncoso JC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 344:769–772.  https://doi.org/10.1016/S0140-6736(94)92338-8 CrossRefPubMedGoogle Scholar
  80. 80.
    Wiersma VI, van Ziel AM, Vazquez-Sanchez S, Nolle A, Berenjeno-Correa E, Bonaterra-Pastra A, et al. (2019) Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology. Acta Neuropathol 138:943-970.  https://doi.org/10.1007/s00401-019-02046-4 CrossRefGoogle Scholar
  81. 81.
    Yamazaki Y, Matsubara T, Takahashi T, Kurashige T, Dohi E, Hiji M, Nagano Y, Yamawaki T, Matsumoto M (2011) Granulovacuolar degenerations appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders. PLoS ONE 6:e26996.  https://doi.org/10.1371/journal.pone.0026996 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Zarow C, Vinters HV, Ellis WG, Weiner MW, Mungas D, White L, Chui HC (2005) Correlates of hippocampal neuron number in Alzheimer’s disease and ischemic vascular dementia. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc 57:896–903.  https://doi.org/10.1002/ana.20503 CrossRefGoogle Scholar
  83. 83.
    Zhang D-W, Shao J, Lin J, Zhang N, Lu B-J, Lin S-C, Dong M-Q, Han J (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336.  https://doi.org/10.1126/science.1172308 CrossRefPubMedGoogle Scholar
  84. 84.
    Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, Liu Z-G (2012) Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci 109:5322–5327.  https://doi.org/10.1073/pnas.1200012109 CrossRefPubMedGoogle Scholar
  85. 85.
    Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 12:723.  https://doi.org/10.1038/nrn3114 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Laboratory for Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI)KU Leuven (University of Leuven)LeuvenBelgium
  2. 2.Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI)KU Leuven (University of Leuven)LeuvenBelgium
  3. 3.Center for Brain and Disease ResearchVIBLeuvenBelgium
  4. 4.Laboratory for Neurobiology, Department of Neurosciences, Leuven Brain Institute (LBI)KU Leuven (University of Leuven)LeuvenBelgium
  5. 5.Department of Neurosciences, Experimental Neurology GroupKU LeuvenLeuvenBelgium
  6. 6.Department of NeurologyUZ LeuvenLeuvenBelgium
  7. 7.Department of Geriatric PsychiatryUniversity Hospitals LeuvenLeuvenBelgium
  8. 8.Department of NeurologyUniversity of UlmUlmGermany
  9. 9.Department of GeriatricsUniversity Medical Center GöttingenGöttingenGermany
  10. 10.Department of PathologyUniversity Hospital LeuvenLeuvenBelgium
  11. 11.Department of PathologyUniversity Hospital LeuvenLeuvenBelgium

Personalised recommendations