Acta Neuropathologica

, Volume 116, Issue 1, pp 103–118 | Cite as

MAPT S305I mutation: implications for argyrophilic grain disease

  • Gabor G. Kovacs
  • Alan Pittman
  • Tamas ReveszEmail author
  • Connie Luk
  • Andrew Lees
  • Eva Kiss
  • Peter Tariska
  • Lajos Laszlo
  • Kinga Molnár
  • Maria J. Molnar
  • Markus Tolnay
  • Rohan de Silva
Case Report


Frontotemporal lobar degeneration (FTLD) with mutations in the tau gene (MAPT) causes familial frontotemporal dementia with tau pathology. Many of these mutations result in morphological phenotypes resembling sporadic tauopathies, although, to date, no such cases mimicking argyrophilic grain disease (AgD) have been documented. We now present a case with a novel S305I MAPT mutation and a morphological phenotype showing resemblance to AgD. At the age of 39, the patient developed behavioural and personality changes and lack of verbal fluency with later poor performance on naming tasks and rigidity in the extremities. After a short disease course of 1.5 years, the patient died. A unique neuropathological phenotype with neuronal diffuse cytoplasmic tau immunoreactivity, oligodendroglial-coiled bodies, argyrophilic grains, and non-argyrophilic, but tau-immunopositive and ubiquitin-immunonegative pre-grains were observed, whereas classical neurofibrillary tangles, Pick bodies, and neuritic plaques were absent. The tau-positive abnormal structures were composed only of 4R-tau isoforms and, ultrastructurally, straight filaments. Neuronal loss was greatest in the medial temporal cortex, hippocampus, and amygdala. These pathological features resemble AgD. The novel S305I substitution has a strong effect on MAPT exon 10 splicing, thereby causing a striking increase in 4R-tau isoforms. Our observation not only widens the phenotypic spectrum of FTLD with MAPT mutation but also underpins the notion that the predominance of similar neuropathological findings in sporadic AgD cases may be viewed as features of a distinct disease entity.


Tau Mutation Argyrophilic grain Frontotemporal lobar degeneration 



This work was supported by a grant from the Reta Lila Weston Trust for Medical Research (RdS, AP, CL, AJL), the PSP (Europe) Association (RdS, CL, AJL, TR), the Medical Research Council (RdS; Grant G0501560), the EU Grant FP6, BNEII No LSHM-CT-2004-503039 (GGK) and the Swiss National Science Foundation Grant 3100-068328 (MT), Alzheimer’s Research Trust (TR) and the Parkinson’s Disease Society (TR).


  1. 1.
    Arima K (2006) Ultrastructural characteristics of tau filaments in tauopathies: immuno-electronmicroscopic demonstration of tau filaments in tauopathies. Neuropathology 26:475–483PubMedCrossRefGoogle Scholar
  2. 2.
    Baker M, Litvan I, Houlden H, Adamson J, Dickson D, Perez-Tur J, Hardy J, Lynch T, Bigio E, Hutton M (1999) Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 8:711–715PubMedCrossRefGoogle Scholar
  3. 3.
    Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Tau and ubiquitin immunoreactivity at different stages of formation of Alzheimer neurofibrillary tangles. Prog Clin Biol Res 317:837–848PubMedGoogle Scholar
  4. 4.
    Braak E, Braak H, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol (Berl) 87:554–567CrossRefGoogle Scholar
  5. 5.
    Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15:13–26PubMedCrossRefGoogle Scholar
  6. 6.
    Brown J, Lantos PL, Roques P, Fidani L, Rossor MN (1996) Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies: a clinical and pathological study. J Neurol Sci 135:21–30PubMedCrossRefGoogle Scholar
  7. 7.
    Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL III, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol (Berl) 114:5–22CrossRefGoogle Scholar
  8. 8.
    D’Souza I, Poorkaj P, Hong M, Nochlin D, Lee VM, Bird TD, Schellenberg GD (1999) Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc Natl Acad Sci USA 96:5598–5603PubMedCrossRefGoogle Scholar
  9. 9.
    de Silva R, Lashley T, Gibb G, Hanger D, Hope A, Reid A, Bandopadhyay R, Utton M, Strand C, Jowett T, Khan N, Anderton B, Wood N, Holton J, Revesz T, Lees A (2003) Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol Appl Neurobiol 29:288–302PubMedCrossRefGoogle Scholar
  10. 10.
    de Silva R, Lashley T, Revesz T, Lees A, Powers JM (2004) Detecting tau isoforms in archival cases. Acta Neuropathol (Berl) 107:181–182CrossRefGoogle Scholar
  11. 11.
    de Silva R, Lashley T, Strand C, Shiarli AM, Shi J, Tian J, Bailey KL, Davies P, Bigio EH, Arima K, Iseki E, Murayama S, Kretzschmar H, Neumann M, Lippa C, Halliday G, MacKenzie J, Ravid R, Dickson D, Wszolek Z, Iwatsubo T, Pickering-Brown SM, Holton J, Lees A, Revesz T, Mann DM (2006) An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies. Acta Neuropathol (Berl) 111:329–340CrossRefGoogle Scholar
  12. 12.
    Dickson DW (1999) Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol 246(Suppl 2):II6–I15PubMedCrossRefGoogle Scholar
  13. 13.
    Fujino Y, Wang DS, Thomas N, Espinoza M, Davies P, Dickson DW (2005) Increased frequency of argyrophilic grain disease in Alzheimer disease with 4R tau-specific immunohistochemistry. J Neuropathol Exp Neurol 64:209–214PubMedGoogle Scholar
  14. 14.
    Ghetti B, Hutton ML, Wszolek ZK (2003) Frontotemporal dementia and parkinsonism linked to chromosome 17 associated with tau gene mutations (FTDP-17T). In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 86–102Google Scholar
  15. 15.
    Goedert M, Jakes R (2005) Mutations causing neurodegenerative tauopathies. Biochim Biophys Acta 1739:240–250PubMedGoogle Scholar
  16. 16.
    Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Science 314:777–781PubMedCrossRefGoogle Scholar
  17. 17.
    Goedert M, Spillantini MG, Cairns NJ, Crowther RA (1992) Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8:159–168PubMedCrossRefGoogle Scholar
  18. 18.
    Grover A, England E, Baker M, Sahara N, Adamson J, Granger B, Houlden H, Passant U, Yen SH, DeTure M, Hutton M (2003) A novel tau mutation in exon 9 (1260 V) causes a four-repeat tauopathy. Exp Neurol 184:131–140PubMedCrossRefGoogle Scholar
  19. 19.
    Halliday GM, Song YJ, Creasey H, Morris JG, Brooks WS, Kril JJ (2006) Neuropathology in the S305S tau gene mutation. Brain 129:E40PubMedCrossRefGoogle Scholar
  20. 20.
    Hanger DP, Gibb GM, de Silva R, Boutajangout A, Brion JP, Revesz T, Lees AJ, Anderton BH (2002) The complex relationship between soluble and insoluble tau in tauopathies revealed by efficient dephosphorylation and specific antibodies. FEBS Lett 531:538–542PubMedCrossRefGoogle Scholar
  21. 21.
    Hasegawa M, Smith MJ, Iijima M, Tabira T, Goedert M (1999) FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10. FEBS Lett 443:93–96PubMedCrossRefGoogle Scholar
  22. 22.
    Hodges JR, Davies RR, Xuereb JH, Casey B, Broe M, Bak TH, Kril JJ, Halliday GM (2004) Clinicopathological correlates in frontotemporal dementia. Ann Neurol 56:399–406PubMedCrossRefGoogle Scholar
  23. 23.
    Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705PubMedCrossRefGoogle Scholar
  24. 24.
    Iijima M, Tabira T (1999) Frontotemporal dementia with tauopathy: a review and preliminary immunohistochemical study of tau kinases and phosphatases. Neuropathology 19:433–440CrossRefGoogle Scholar
  25. 25.
    Iijima M, Tabira T, Poorkaj P, Schellenberg GD, Trojanowski JQ, Lee VM, Schmidt ML, Takahashi K, Nabika T, Matsumoto T, Yamashita Y, Yoshioka S, Ishino H (1999) A distinct familial presenile dementia with a novel missense mutation in the tau gene. Neuroreport 10:497–501PubMedCrossRefGoogle Scholar
  26. 26.
    Ikeda K, Akiyama H, Arai T, Matsushita M, Tsuchiya K, Miyazaki H (2000) Clinical aspects of argyrophilic grain disease. Clin Neuropathol 19:278–284PubMedGoogle Scholar
  27. 27.
    Ingram EM, Spillantini MG (2002) Tau gene mutations: dissecting the pathogenesis of FTDP-17. Trends Mol Med 8:555–562PubMedCrossRefGoogle Scholar
  28. 28.
    Iseki E, Matsumura T, Marui W, Hino H, Odawara T, Sugiyama N, Suzuki K, Sawada H, Arai T, Kosaka K (2001) Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in exon 10 of the tau gene and a widespread tau accumulation in the glial cells. Acta Neuropathol (Berl) 102:285–292Google Scholar
  29. 29.
    Josephs KA, Whitwell JL, Parisi JE, Knopman DS, Boeve BF, Geda YE, Jack CR, Jr, Petersen RC, Dickson DW (2006) Argyrophilic grains: a distinct disease or an additive pathology? Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2006.10.032
  30. 30.
    Kobayashi K, Hayashi M, Kidani T, Ujike H, Iijima M, Ishihara T, Nakano H, Sugimori K, Shimazaki M, Kuroda S, Koshino Y (2004) Pick’s disease pathology of a missense mutation of S305N of frontotemporal dementia and parkinsonism linked to chromosome 17: another phenotype of S305N. Dement Geriatr Cogn Disord 17:293–297PubMedCrossRefGoogle Scholar
  31. 31.
    Kobayashi K, Kidani T, Ujike H, Hayashi M, Ishihara T, Miyazu K, Kuroda S, Koshino Y (2003) Another phenotype of frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17) with a missense mutation of S305N closely resembling Pick’s disease. J Neurol 250:990–992PubMedCrossRefGoogle Scholar
  32. 32.
    Lantos PL, Cairns NJ, Khan MN, King A, Revesz T, Janssen JC, Morris H, Rossor MN (2002) Neuropathologic variation in frontotemporal dementia due to the intronic tau 10(+16) mutation. Neurology 58:1169–1175PubMedGoogle Scholar
  33. 33.
    Lippa CF, Zhukareva V, Kawarai T, Uryu K, Shafiq M, Nee LE, Grafman J, Liang Y, St George-Hyslop PH, Trojanowski JQ, Lee VM (2000) Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation. Ann Neurol 48:850–858PubMedCrossRefGoogle Scholar
  34. 34.
    Maurage CA, Sergeant N, Schraen-Maschke S, Lebert F, Ruchoux MM, Sablonniere B, Pasquier F, Delacourte A (2003) Diffuse form of argyrophilic grain disease: a new variant of four-repeat tauopathy different from limbic argyrophilic grain disease. Acta Neuropathol (Berl) 106:575–583CrossRefGoogle Scholar
  35. 35.
    McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ (2001) Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 58:1803–1809PubMedCrossRefGoogle Scholar
  36. 36.
    Momeni P, Pittman A, Lashley T, Vandrovcova J, Malzer E, Luk C, Hulette C, Lees A, Revesz T, Hardy J, de Silva R (2007) Clinical and pathological features of an Alzheimer’s disease patient with the MAPT D280K mutation. Neurobiol Aging. doi: 10.1016/jneurobiolaging.2007.07.013
  37. 37.
    Morris HR, Khan MN, Janssen JC, Brown JM, Perez-Tur J, Baker M, Ozansoy M, Hardy J, Hutton M, Wood NW, Lees AJ, Revesz T, Lantos P, Rossor MN (2001) The genetic and pathological classification of familial frontotemporal dementia. Arch Neurol 58:1813–1816PubMedCrossRefGoogle Scholar
  38. 38.
    Neumann M, Mittelbronn M, Simon P, Vanmassenhove B, de Silva R, Lees A, Klapp J, Meyermann R, Kretzschmar HA (2005) A new family with frontotemporal dementia with intronic 10 + 3 splice site mutation in the tau gene: neuropathology and molecular effects. Neuropathol Appl Neurobiol 31:362–373PubMedCrossRefGoogle Scholar
  39. 39.
    Pickering-Brown SM, Richardson AM, Snowden JS, McDonagh AM, Burns A, Braude W, Baker M, Liu WK, Yen SH, Hardy J, Hutton M, Davies Y, Allsop D, Craufurd D, Neary D, Mann DM (2002) Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain 125:732–751PubMedCrossRefGoogle Scholar
  40. 40.
    Pittman AM, Fung HC, de Silva R (2006) Untangling the tau gene association with neurodegenerative disorders. Hum Mol Genet 15 Spec No 2:R188–R195PubMedCrossRefGoogle Scholar
  41. 41.
    Rademakers R, Cruts M, van Broeckhoven C (2004) The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat 24:277–295PubMedCrossRefGoogle Scholar
  42. 42.
    Ros R, Thobois S, Streichenberger N, Kopp N, Sanchez MP, Perez M, Hoenicka J, Avila J, Honnorat J, de Yebenes JG (2005) A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy. Arch Neurol 62:1444–1450PubMedCrossRefGoogle Scholar
  43. 43.
    Saito Y, Nakahara K, Yamanouchi H, Murayama S (2002) Severe involvement of ambient gyrus in dementia with grains. J Neuropathol Exp Neurol 61:789–796PubMedGoogle Scholar
  44. 44.
    Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, Yamanouchi H, Murayama S (2004) Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol 63:911–918PubMedGoogle Scholar
  45. 45.
    Spillantini MG, Goedert M (2000) Tau mutations in familial frontotemporal dementia. Brain 123(Pt 5):857–859PubMedCrossRefGoogle Scholar
  46. 46.
    Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MR, Ghetti B (1997) Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments. Proc Natl Acad Sci USA 94:4113–4118PubMedCrossRefGoogle Scholar
  47. 47.
    Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B (1998) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci USA 95:7737–7741PubMedCrossRefGoogle Scholar
  48. 48.
    Spillantini MG, Yoshida H, Rizzini C, Lantos PL, Khan N, Rossor MN, Goedert M, Brown J (2000) A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies. Ann Neurol 48:939–943PubMedCrossRefGoogle Scholar
  49. 49.
    Stanford PM, Halliday GM, Brooks WS, Kwok JB, Storey CE, Creasey H, Morris JG, Fulham MJ, Schofield PR (2000) Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations. Brain 123(Pt 5):880–893PubMedCrossRefGoogle Scholar
  50. 50.
    Stanford PM, Shepherd CE, Halliday GM, Brooks WS, Schofield PW, Brodaty H, Martins RN, Kwok JB, Schofield PR (2003) Mutations in the tau gene that cause an increase in three repeat tau and frontotemporal dementia. Brain 126:814–826PubMedCrossRefGoogle Scholar
  51. 51.
    Takamatsu J, Kondo A, Ikegami K, Kimura T, Fujii H, Mitsuyama Y, Hashizume Y (1998) Selective expression of Ser 199/202 phosphorylated tau in a case of frontotemporal dementia. Dement Geriatr Cogn Disord 9:82–89PubMedCrossRefGoogle Scholar
  52. 52.
    Thal DR, Schultz C, Botez G, Del Tredici K, Mrak RE, Griffin WS, Wiestler OD, Braak H, Ghebremedhin E (2005) The impact of argyrophilic grain disease on the development of dementia and its relationship to concurrent Alzheimer’s disease-related pathology. Neuropathol Appl Neurobiol 31:270–279PubMedCrossRefGoogle Scholar
  53. 53.
    Togo T, Isojima D, Akatsu H, Suzuki K, Uchikado H, Katsuse O, Iseki E, Kosaka K, Hirayasu Y (2005) Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms. Am J Geriatr Psychiatry 13:1083–1091PubMedCrossRefGoogle Scholar
  54. 54.
    Togo T, Sahara N, Yen SH, Cookson N, Ishizawa T, Hutton M, de Silva R, Lees A, Dickson DW (2002) Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J Neuropathol Exp Neurol 61:547–556PubMedGoogle Scholar
  55. 55.
    Tolnay M, Clavaguera F (2004) Argyrophilic grain disease: a late-onset dementia with distinctive features among tauopathies. Neuropathology 24:269–283PubMedCrossRefGoogle Scholar
  56. 56.
    Tolnay M, Grazia Spillantini M, Rizzini C, Eccles D, Lowe J, Ellison D (2000) A new case of frontotemporal dementia and parkinsonism resulting from an intron 10 +3-splice site mutation in the tau gene: clinical and pathological features. Neuropathol Appl Neurobiol 26:368–378PubMedCrossRefGoogle Scholar
  57. 57.
    Tolnay M, Mistl C, Ipsen S, Probst A (1998) Argyrophilic grains of Braak: occurrence in dendrites of neurons containing hyperphosphorylated tau protein. Neuropathol Appl Neurobiol 24:53–59PubMedGoogle Scholar
  58. 58.
    Tsuchiya K, Mitani K, Arai T, Yamada S, Komiya T, Esaki Y, Haga C, Yamanouchi H, Ikeda K (2001) Argyrophilic grain disease mimicking temporal Pick’s disease: a clinical, radiological, and pathological study of an autopsy case with a clinical course of 15 years. Acta Neuropathol (Berl) 102:195–199Google Scholar
  59. 59.
    Wszolek ZK, Slowinski J, Golan M, Dickson DW (2005) Frontotemporal dementia and parkinsonism linked to chromosome 17. Folia Neuropathol 43:258–270PubMedGoogle Scholar
  60. 60.
    Wszolek ZK, Tsuboi Y, Ghetti B, Pickering-Brown S, Baba Y, Cheshire WP (2006) Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Orphanet J Rare Dis 1:30PubMedCrossRefGoogle Scholar
  61. 61.
    Wszolek ZK, Tsuboi Y, Uitti RJ, Reed L, Hutton ML, Dickson DW (2001) Progressive supranuclear palsy as a disease phenotype caused by the S305S tau gene mutation. Brain 124:1666–1670PubMedCrossRefGoogle Scholar
  62. 62.
    Yao TM, Tomoo K, Ishida T, Hasegawa H, Sasaki M, Taniguchi T (2003) Aggregation analysis of the microtubule binding domain in tau protein by spectroscopic methods. J Biochem (Tokyo) 134:91–99Google Scholar
  63. 63.
    Yasuda M, Kawamata T, Komure O, Kuno S, D’Souza I, Poorkaj P, Kawai J, Tanimukai S, Yamamoto Y, Hasegawa H, Sasahara M, Hazama F, Schellenberg GD, Tanaka C (1999) A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration. Neurology 53:864–868PubMedGoogle Scholar
  64. 64.
    Yasuda M, Takamatsu J, D’Souza I, Crowther RA, Kawamata T, Hasegawa M, Hasegawa H, Spillantini MG, Tanimukai S, Poorkaj P, Varani L, Varani G, Iwatsubo T, Goedert M, Schellenberg DG, Tanaka C (2000) A novel mutation at position +12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTD-Kumamoto). Ann Neurol 47:422–429PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Gabor G. Kovacs
    • 1
    • 8
  • Alan Pittman
    • 2
  • Tamas Revesz
    • 3
    Email author
  • Connie Luk
    • 2
  • Andrew Lees
    • 2
  • Eva Kiss
    • 4
  • Peter Tariska
    • 4
  • Lajos Laszlo
    • 5
  • Kinga Molnár
    • 5
  • Maria J. Molnar
    • 6
  • Markus Tolnay
    • 7
  • Rohan de Silva
    • 2
  1. 1.Institute of NeurologyMedical University of ViennaViennaAustria
  2. 2.Reta Lila Weston Institute of Neurological Studies and Department of Molecular NeuroscienceUCL Institute of NeurologyLondonUK
  3. 3.Department of Molecular Neuroscience, Queen Square Brain BankUCL Institute of NeurologyLondonUK
  4. 4.National Insitute of Psychiatry and Neurology, Memory ClinicBudapestHungary
  5. 5.Department of Anatomy, Cell and Developmental BiologyEotvos Lorand University of SciencesBudapestHungary
  6. 6.Department of Molecular NeurologyNational Insitute of Psychiatry and NeurologyBudapestHungary
  7. 7.Institute of Pathology, Department of NeuropathologyUniversity Hospital BaselBaselSwitzerland
  8. 8.Department of NeuropathologyNational Insitute of Psychiatry and NeurologyBudapestHungary

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