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01.04.2006 | Original Paper

An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies

verfasst von: Rohan de Silva, Tammaryn Lashley, Catherine Strand, Anna-Maria Shiarli, Jing Shi, Jinzhou Tian, Kathryn L. Bailey, Peter Davies, Eileen H. Bigio, Kunimasa Arima, Eizo Iseki, Shigeo Murayama, Hans Kretzschmar, Manuela Neumann, Carol Lippa, Glenda Halliday, James MacKenzie, Rivka Ravid, Dennis Dickson, Zbigniew Wszolek, Takeshi Iwatsubo, Stuart M. Pickering-Brown, Janice Holton, Andrew Lees, Tamas Revesz, David M. A. Mann

Erschienen in: Acta Neuropathologica | Ausgabe 4/2006

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Abstract

The pathological distinctions between the various clinical and pathological manifestations of frontotemporal lobar degeneration (FTLD) remain unclear. Using monoclonal antibodies specific for 3- and 4-repeat isoforms of the microtubule associated protein, tau (3R- and 4R-tau), we have performed an immunohistochemical study of the tau pathology present in 14 cases of sporadic forms of FTLD, 12 cases with Pick bodies and two cases without and in 27 cases of familial FTLD associated with 12 different mutations in the tau gene (MAPT), five cases with Pick bodies and 22 cases without. In all 12 cases of sporadic FTLD where Pick bodies were present, these contained only 3R-tau isoforms. Clinically, ten of these cases had frontotemporal dementia and two had progressive apraxia. Only 3R-tau isoforms were present in Pick bodies in those patients with familial FTLD associated with L266V, Q336R, E342V, K369I or G389R MAPT mutations. Patients with familial FTLD associated with exon 10 N279K, N296H or +16 splice site mutations showed tau pathology characterised by neuronal neurofibrillary tangles (NFT) and glial cell tangles that contained only 4R-tau isoforms, as did the NFT in P301L MAPT mutation. With the R406W mutation, NFT contained both 3R- and 4R-tau isoforms. We also observed two patients with sporadic FTLD, but without Pick bodies, in whom the tau pathology comprised only of 4R-tau isoforms. We have therefore shown by immunohistochemistry that different specific tau isoform compositions underlie the various kinds of tau pathology present in sporadic and familial FTLD. The use of such tau isoform specific antibodies may refine pathological criteria underpinning FTLD.

Arai T, Ikeda K, Akiyama H, Shikamoto Y, Tsuchiya K, Yagishita S, Beach T, Rogers J, Schwab C, McGeer PL (2001) Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick’s disease, corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol 101:167–173PubMed

Arima K, Kowalska A, Hasegawa M, Mukoyama M, Watanabe R, Kawai M, Takahashi K, Iwatsubo T, Tabira T, Sunohara N (2000) Two brothers with frontotemporal dementia and parkinsonism with an N279K mutation of the tau gene. Neurology 54:1787–1795PubMed

Bird TD, Nochlin D, Poorkaj P, Cherrier M, Kaye J, Payami H, Peskind E, Lampe TH, Nemens E, Boyer P, Schellenberg GD (1999) A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain 122:741–756CrossRefPubMed

Bronner IF, ter Meulen BC, Azmani A, Severijnen LA, Willemsen R, Kamphorst W, Ravid R, Heutink P, van Swieten JC (2005) Hereditary Pick’s disease with the G272V tau mutation shows a predominant three-repeat tau pathology. Brain 128:2645–2653CrossRefPubMed

Bugiani O, Murrell JR, Giaccone G, Hasegawa M, Ghigo G, Tabaton M, Morbin M, Primavera A, Carella F, Solaro C, Grisoli M, Savoiardo M, Spillantini MG, Tagliavini F, Goedert M, Ghetti B (1999) Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J Neuropathol Exp Neurol 58:667–677PubMedCrossRef

Clark LN, Poorkaj P, Wszolek Z, Geschwind DH, Nasreddine ZS, Miller B, Li D, Payami H, Awert F, Markopoulou K, Andreadis A, D’Souza I, Lee VM, Reed L, Trojanowski JQ, Zhukareva V, Bird T, Schellenberg G, Wilhelmsen KC (1998) Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17. Proc Natl Acad Sci USA 95:13103–13107CrossRefPubMed

Constantinidis RJ, Richard J, Tissot R (1974) Pick’s disease: histological and clinical correlations. Eur Neurol 11:208–217PubMedCrossRef

Delacourte A, Sergeant N, Wattez A, Gauvreau D, Robitaille Y (1998) Vulnerable neuronal subsets in Alzheimer’s and Pick’s disease are distinguished by their tau isoform distribution and phosphorylation. Ann Neurol 43:193–204CrossRefPubMed

Delisle MB, Murrell JR, Richardson R, Trofatter JA, Rascol O, Soulages X, Mohr M, Calvas P, Ghetti B (1999) A mutation at codon 279 (N279K) in exon 10 of the tau gene causes a tauopathy with dementia and supranuclear palsy. Acta Neuropathol 98:62–77CrossRefPubMed

10.

de Silva R, Lashley T, Gibb G, 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 29:288–302CrossRefPubMed

11.

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 96:5598–5603CrossRefPubMed

12.

Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D’Amato CJ, Gilman S (1997) Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Ann Neurol 41:706–715CrossRefPubMed

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 64:209–214PubMed

14.

Ghetti B, Murrell JR, Zolo P, Spillantini MG, Goedert M (2000) Progress in hereditary tauopathies: a mutation in the tau gene (G389R) causes a Pick disease-like syndrome. Ann N Y Acad Sci 920:52–62PubMedCrossRef

15.

Goedert M (2005) Tau gene mutations and their effects. Mov Disord 20(Suppl 12):S45–S52CrossRefPubMed

16.

Goedert M, Jakes R, Crowther RA, Six J, Lubke U, Vandermeeren M, Cras P, Trojanowski JQ, Lee VM (1993) The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. Proc Natl Acad Sci USA 90:5066–5070PubMedCrossRef

17.

Goedert M, Spillantini MG, Crowther RA, Chen SG, Parchi P, Tabaton M, Lanska DJ, Markesbery WR, Wilhelmsen KC, Dickson DW, Petersen PB, Gambetti P (1999). Tau gene mutation in familial progressive subcortical gliosis. Nat Med 5:454–457CrossRefPubMed

18.

Grover A, DeTure M, Yen SH, Hutton M (2002) Effects on splicing and protein function of three mutations in codon N296 of tau in vitro. Neurosci Lett 323:33–36CrossRefPubMed

19.

Halliday GM, Song YJC, Creasey H, Morris JG, Brooks WS, Kril JJ (2006) Neuropathology in the S305S tau gene mutation. Brain (in press)

20.

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 443:93–96CrossRefPubMed

21.

Hayashi S, Toyoshima Y, Hasegawa M, Umeda Y, Wakabayashi K, Tokiguchi S, Iwatsubo T, Takahashi H (2002) Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Ann Neurol 51:525–530CrossRefPubMed

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 56:399–406CrossRefPubMed

23.

Hogg M, Grujic ZM, Baker M, Demirci S, Guillozet AL, Sweet AP, Herzog LL, Weintraub S, Mesulam MM, LaPointe NE, Gamblin TC, Berry RW, Binder LI, de Silva R, Lees A, Espinoza M, Davies P, Grover A, Sahara N, Ishizawa T, Dickson D, Yen SH, Hutton M, Bigio EH (2003) The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy. Acta Neuropathol 106:323–336CrossRefPubMed

24.

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 MJ, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski JQ, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JBJ, 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 393:702–705PubMedCrossRef

25.

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 102:285–292PubMed

26.

Ishizawa K, Ksiezak-Reding H, Davies P, Delacourte A, Tiseo P, Yen S-H, Dickson DW (2000) A double-labelling immunohistochemical study of tau exon 10 in Alzheimer’s disease, progressive supranuclear palsy and Pick’s disease. Acta Neuropathol 100:235–244CrossRefPubMed

27.

Ishizawa T, Ko LW, Cookson N, Davies P, Espinoza M, Dickson DW (2002) Selective neurofibrillary degeneration of the hippocampal CA2 sector is associated with four repeat tauopathies. J Neuropathol Exp Neurol 61:1040–1047PubMed

28.

Kertesz A, McGonagle P, Blair M, Davidson W, Munoz DG (2005) The evolution and pathology of frontotemporal dementia. Brain 128:1996–2005CrossRefPubMed

29.

Kobayashi T, Ota S, Tanaka K, Ito Y, Hasegawa M, Umeda Y, Motoi Y, Takanashi M, Yasuhara M, Anno M, et al (2003) A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology. Ann Neurol 53:133–137CrossRefPubMed

30.

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 48:850–858CrossRefPubMed

31.

Lipton AM, White CL III, Bigio EH (2004) Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration. Acta Neuropathol 108:379–385CrossRefPubMed

32.

Mann DMA (2005) The genetics and molecular pathology of frontotemporal lobar degeneration. In: Burns A, O’Brien J, Ames D, Arnold H (eds) Dementia, 3rd edn. , London, pp 689–701

33.

Mann DMA, South PW, Snowden JS, Neary D (1993) Dementia of frontal lobe type: neuropathology and immunohistochemistry. J Neurol Neurosur Ps 56:605–614CrossRef

34.

McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ (2001) Workgroup on Frontotemporal dementia and Picks disease; Clinical and pathological diagnosis of frontotemporal dementia: report of the workgroup on Frontotemporal dementia and Picks disease. Arch Neurol 59:1203–1204

35.

Mirra SS, Murrell JR, Gearing M, Spillantini MG, Goedert M, Crowther RA, Levey AI, Jones R, Green J, Shoffner JM, Wainer BH, Schmidt ML, Trojanowski JQ, Ghetti B (1999) Tau pathology in a family with dementia and a P301L mutation in tau. J Neuropathol Exp Neurol 58:335–345PubMedCrossRef

36.

Miyasaka T, Morishima-Kawashima M, Ravid R, Kamphorst W, Nagashima K, Ihara Y (2001) Selective deposition of mutant tau in the FTDP-17 brain affected by the P301L mutation. J Neuropathol Exp Neurol 60:872–884PubMed

37.

Motoi Y, Iwamoto H, Itaya M, Kobayashi T, Hasegawa M, Yasuda M, Mizuno Y, Mori H (2005) Four-repeat tau positive Pick body-like inclusions are distinct from classic Pick bodies. Acta Neuropathol 110:431–433CrossRefPubMed

38.

Mott RT, Dickson DW, Trojanowski JQ, Zhukareva V, Lee VM, Forman M, van Deerlin V, Ervin JF, Wang DS, Schmechel DE, Hulette CM (2005) Neuropathologic, biochemical, and molecular characterization of the frontotemporal dementias. J Neuropathol Exp Neurol 64:420–428PubMed

39.

Murrell JR, Spillantini MG, Zolo P, Guazzelli M, Smith MJ, Hasegawa M, Redi F, Crowther RA, Pietrini P, Ghetti B, Goedert M (1999) Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J Neuropathol Exp Neurol 58:1207–1226PubMedCrossRef

40.

Nasreddine ZS, Loginov M, Clark LN, Lamarche J, Miller BL, Lamontagne A, Zhukareva V, Lee VM, Wilhelmsen KC, Geschwind DH (1999) From genotype to phenotype: a clinical pathological, and biochemical investigation of frontotemporal dementia and parkinsonism (FTDP-17) caused by the P301L tau mutation. Ann Neurol 45:704–715CrossRefPubMed

41.

Neary D, Snowden JS, Mann DMA (2005) Frontotemporal dementia. Lancet Neurol 4:771–780CrossRefPubMed

42.

Neumann M, Schulz-Schaeffer W, Crowther RA, Smith MJ, Spillantini MG, Goedert M, Kretzschmar HA (2001) Pick’s disease associated with the novel Tau gene mutation K369I. Ann Neurol 50:503–513CrossRefPubMed

43.

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 31:362–373CrossRefPubMed

44.

Papasozomenos SC (1989) Tau protein immunoreactivity in dementia of the Alzheimer type: II. Electron microscopy and pathogenetic implications. Effects of fixation on the morphology of the Alzheimer’s abnormal filaments. Lab Invest 60:375–389PubMed

45.

Pickering-Brown SM, Baker M, Yen S-H, Liu W-K, Hasegawa M, Cairns NJ, Lantos PL, Rossor M, Iwatsubo T, Davies Y, Allsop D, Furlong R, Owen F, Hardy J, Mann DMA, Hutton M (2000) Pick’s disease is associated with mutations in the tau gene. Ann Neurol 48:859–867CrossRefPubMed

46.

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 DMA (2002) Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain 125:732–751CrossRefPubMed

47.

Pickering-Brown SM, Baker M, Nonaka T, Ikeda K, Sharma S, MacKenzie J, Simpson SA, Moore JW, Snowden JS, de Silva R, Revesz T, Hasegawa M, Hutton M, Mann DM (2004) Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene. Brain 127:1415–1426CrossRefPubMed

48.

Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Wiederholt WC, Raskind M, Schellenberg GD (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 43:815–825CrossRefPubMed

49.

Reed LA, Grabowski TJ, Schmidt ML (1997) Autosomal dominant dementia with widespread neurofibrillary tangles. Ann Neurol 42:564–572CrossRefPubMed

50.

Rizzini C, Goedert M, Hodges JR, Smith MJ, Jakes R, Hills R, Xuereb JH, Crowther RA, Spillantini MG (2000) Tau gene mutation K257T causes a tauopathy similar to Pick’s disease. J Neuropathol Exp Neurol 59:990–1001PubMed

51.

Rizzu P, van Swieten JC, Joosse M, Hasegawa M, Stevens M, Tibben A, Niermeijer MF, Hillebrand M, Ravid R, Oostra BA, Goedert M, van Duijn CM, Heutink P (1999) High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am J Hum Genet 64:414–421CrossRefPubMed

52.

Rosso SM, van Herpen E, Deelen W, Kamphorst W, Severijnen LA, Willemsen R, Ravid R, Niermeijer MF, Dooijes D, Smith MJ, Goedert M, Heutink P, van Swieten JC (2002) A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick’s disease. Ann Neurol 51:373–376CrossRefPubMed

53.

Rosso SM, Landweer EJ, Houterman M, Donker Kaat L, van Duijn CM, van Swieten JC (2003) Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study. J Neurol Neurosur Ps 74:1574–1576CrossRef

54.

Sergeant N, Wattez A, Delacourte A (1999) Neurofibrillary degeneration in progressive supranuclear palsy and corticobasal degeneration: tau pathologies with exclusively exon 10 isoforms. J Neurochem 72:1243–1249PubMedCrossRef

55.

Shi J, Shaw CL, Du Plessis D, Richardson AMT, Bailey K, Julien C, Neary D, Snowden JS, Mann DMA (2005) Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation. Acta Neuropathol 110:501–512CrossRefPubMed

56.

Snowden JS, Neary D, Mann DMA (1996) Fronto-temporal lobar degeneration: Fronto-temporal dementia, progressive aphasia, semantic dementia. Churchill Livingstone, Edinburgh, pp 1–227

57.

Spillantini MG, Crowther RA, Goedert M (1996) Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial presenile dementia with tangles. Acta Neuropathol 92:42–48CrossRefPubMed

58.

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 95:7737–7741CrossRefPubMed

59.

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 48:939–943CrossRefPubMed

60.

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 123:880–893CrossRefPubMed

61.

Sumi SM, Bird TD, Nochlin D, Raskind MA (1992) Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala. Neurology 42:120–127PubMed

62.

Taniguchi S, McDonagh AM, Pickering-Brown SM, Umeda Y, Iwatsubo T, Hasegawa M, Mann DM (2004) The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein. Neuropathol Appl Neurobiol 30:1–18CrossRefPubMed

63.

van Swieten JC, Stevens M, Rosso SM, Rizzu P, Joosse M, de Koning I, Kamphorst W, Ravid R, Spillantini MG, Niermeijer M, Heutink P (1999) Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann Neurol 46:617–626CrossRefPubMed

64.

Wszolek ZK, Pfeiffer RF, Bhatt MH, Schelper RL, Cordes M, Snow BJ Rodnitsky RL, Wolters EC, Arwert F, Calne DB (1992) Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration. Ann Neurol 32:312–320CrossRefPubMed

65.

Zarrantz JJ, Ferrer I, Lezcano E, Forcadas MI, Eizaguirre B, Atares B, Puig B, Gomez-Esteban JC, Fernandez-Maiztegui C, Rouco I, Perez-Concha T, Fernandez M, Rodruigez O, Rodriguez-Martinez AB, Martinez de Pancorbo M, Pastor P, Perez-Tur J (2005) A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease. Neurology 64:1578–1585PubMedCrossRef

66.

Zhukareva V, Mann DMA, Uryu K, Shuck T, Shah K, Grossman M, Miller BL, Hulette CM, Feinstein S, Trojanowski JQ, Lee VM-Y (2002) Sporadic Pick’s disease: a tauopathy characterised by a spectrum of gray and white matter pathological tau isoforms. Ann Neurol 51:730–739CrossRefPubMed

Titel: An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies
verfasst von: Rohan de Silva
Tammaryn Lashley
Catherine Strand
Anna-Maria Shiarli
Jing Shi
Jinzhou Tian
Kathryn L. Bailey
Peter Davies
Eileen H. Bigio
Kunimasa Arima
Eizo Iseki
Shigeo Murayama
Hans Kretzschmar
Manuela Neumann
Carol Lippa
Glenda Halliday
James MacKenzie
Rivka Ravid
Dennis Dickson
Zbigniew Wszolek
Takeshi Iwatsubo
Stuart M. Pickering-Brown
Janice Holton
Andrew Lees
Tamas Revesz
David M. A. Mann
Publikationsdatum: 01.04.2006
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 4/2006
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-006-0048-x

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An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies

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