Top

Published in:

01-07-2010 | Original Paper

Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity

Authors: Yong-Juan Fu, Yasushi Nishihira, Shigetoshi Kuroda, Yasuko Toyoshima, Tomohiko Ishihara, Makoto Shinozaki, Akinori Miyashita, Yue-Shan Piao, Chun-Feng Tan, Takashi Tani, Ryoko Koike, Keisuke Iwanaga, Mitsuhiro Tsujihata, Osamu Onodera, Ryozo Kuwano, Masatoyo Nishizawa, Akiyoshi Kakita, Takeshi Ikeuchi, Hitoshi Takahashi

Published in: Acta Neuropathologica | Issue 1/2010

Abstract

Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.

Arai T, Ikeda K, Akiyama H et al (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

Arai T, Ikeda K, Akiyama H et al (2004) Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration. Ann Neurol 55:72–79CrossRefPubMed

Bigio EH, Lipton AM, Yen S-H et al (2001) Frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy with dementia. J Neuropathol Exp Neurol 60:328–341PubMed

Boeve BF, Lang AE, Litvan I (2003) Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol 54(Suppl 5):S15–S19CrossRefPubMed

Boeve BF, Maraganore DM, Parisi JE et al (1999) Pathologic heterogeneity in clinically diagnosed corticobasal degeneration. Neurology 53:795–800PubMed

Buée L, Delacourte A (1999) Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick’s disease. Brain Pathol 9:681–693PubMed

Cairns NJ, Bigio EH, Mackenzie IRA et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol 114:5–22CrossRefPubMed

de Silva R, Lashley T, Gibb G et al (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

Dickson DW (1999) Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol 246(Suppl 2):II6–II15

10.

Dickson DW, Bergeron C, Chin SS et al (2002) Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61:935–946PubMed

11.

Dickson D, Litvan I (2003) Corticobasal degeneration. In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 115–123

12.

Dickson DW, Rademarkers R, Hutton ML (2007) Progressive supranuclear palsy: pathology and genetics. Brain Pathol 17:74–82CrossRefPubMed

13.

Ferrer I, Hernández I, Boada M et al (2003) Primary progressive aphasia as the initial manifestation of corticobasal degeneration and unusual tauopathies. Acta Neuropathol 106:419–435CrossRefPubMed

14.

Ghetti B, Hutton ML, Wszolek ZK (2003) Frontotemporal dementia and Parkinsonism linked to chromosome 17 associated with tau gene mutation (FTDP-17T). In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 86–102

15.

Hauw J-J, Agid Y (2003) Progressive supranuclear palsy (PSP) or Steele-Richardson-Olszewski disease. In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 103–114

16.

Josephs KA, Katsuse O, Beccano-Kelly DA et al (2006) Atypical progressive supranuclear palsy with corticospinal tract degeneration. J Neuropathol Exp Neurol 65:396–405CrossRefPubMed

17.

Katsuse O, Iseki E, Arai T et al (2003) 4-Repeat tauopathy sharing pathological and biochemical features of corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol 106:251–260CrossRefPubMed

18.

Komori T, Arai N, Oda M, Nakayama H et al (1998) Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol 96:401–408CrossRefPubMed

19.

Kovacs GG, Majtenyi K, Spina S et al (2008) White matter tauopathy with globular glial inclusions: a distinct sporadic frontotemporal lobar degeneration. J Neuropathol Exp Neurol 67:963–975CrossRefPubMed

20.

Kuroda S, Otsuki S, Tateishi J, Hirano A (1979) Neurofibrillary degeneration in a case of quadriplegia and myoclonic movement. Acta Neuropathol 45:105–109CrossRefPubMed

21.

Litvan I, Agid Y, Calne D et al (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47:1–9PubMed

22.

Litvan I, Grimes DA, Lang AE (2000) Phenotypes and prognosis: clinicopathologic studies of corticobasal degeneration. Adv Neurol 82:183–196PubMed

23.

Mackenzie IRA, Neumann M, Bigio EH et al (2009) Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 117:15–18CrossRefPubMed

24.

Mackenzie IRA, Neumann M, Bigio EH et al (2010) Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 119:1–4CrossRefPubMed

25.

Martinaud O, Laquerrière A, Guyant-Maréchal L et al (2005) Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family. Acta Neuropathol 110:84–92CrossRefPubMed

26.

Munoz DG, Neumann M, Kusaka H, Yokota O, Ishihara K, Terada S, Kuroda S, Mackenzie IR (2009) FUS pathology in basophilic inclusion body disease. Acta Neuropathol 118:617–627CrossRefPubMed

27.

Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA, Mackenzie IRA (2009) A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain 132:2922–2931CrossRefPubMed

28.

Nishihira Y, Tan CF, Onodera O et al (2008) Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol 116:169–182CrossRefPubMed

29.

Okazaki K, Fu Y-J, Nishihira Y et al (2009) Alzheimer’s disease: report of tow autopsy cases with a clinical diagnosis of corticobasal degeneration. Neuropathology doi:10.1111/j.1440-1789.2009.01062.x

30.

Piao Y-S, Tan C-F, Iwanaga K et al (2005) Sporadic four-repeat tauopathy with frontotemporal degeneration, Parkinsonism and motor neuron disease. Acta Neuropathol 110:600–609CrossRefPubMed

31.

Piao Y-S, Wakabayashi K, Kakita A et al (2003) Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. Brain Pathol 12:10–22

32.

Powers JM, Bryne NP, Ito M et al (2003) A novel leukoencephalopathy associated with tau deposits primarily in white matter glia. Acta Neuropathol 106:181–187CrossRefPubMed

33.

Rizzu P, Van Swieten JC, Joosse M et al (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

34.

Sakai K, Piao Y-S, Kikugawa K et al (2006) Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes. Acta Neuropathol 112:341–348CrossRefPubMed

35.

Spillantini MG, Bird TD, Ghetti B (1998) Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol 8:387–402PubMedCrossRef

36.

Tan C-F, Kakita A, Piao Y-S et al (2003) Primary lateral sclerosis: a rare upper-motor-predominant form of amyotrophic lateral sclerosis often accompanied by frontotemporal lobar degeneration with ubiquitinated neuronal inclusions? Report of an autopsy case and a review of the literature. Acta Neuropathol 105:615–620PubMed

37.

Tan C-F, Piao Y-S, Kakita A et al (2005) Frontotemporal dementia with co-occurrence of astrocytic plaques and tufted astrocytes, and severe degeneration of the cerebral white matter: a variant of corticobasal degeneration? Acta Neuropathol 109:329–338CrossRefPubMed

38.

Uchihara T (2007) Silver diagnosis in neuropathology: principles, practice and revised interpretation. Acta Neuropathol 113:483–499CrossRefPubMed

39.

Uchihara T, Ikeda K, Tsuchiya K (2003) Pick body disease and Pick syndrome. Neuropathology 23:318–326CrossRefPubMed

40.

van Swieten J, Spillantini MG (2007) Hereditary frontotemporal dementia caused by tau gene mutations. Brain Pathol 17:63–73CrossRefPubMed

41.

Yokota O, Tsuchiya K, Oda T et al (2006) Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration. Acta Neuropathol 112:633–645CrossRefPubMed

42.

Zarranz JJ, Ferrer I, Lezcano E et al (2005) A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease. Neurology 64:1578–1585CrossRefPubMed

43.

Zhukareva V, Mann D, Pickering-Brown S et al (2002) Sporadic Pick’s disease: a tauopathy characterized by a spectrum of pathological τ isoforms in gray and white matter. Ann Neurol 51:730–739CrossRefPubMed

Title: Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity
Authors: Yong-Juan Fu
Yasushi Nishihira
Shigetoshi Kuroda
Yasuko Toyoshima
Tomohiko Ishihara
Makoto Shinozaki
Akinori Miyashita
Yue-Shan Piao
Chun-Feng Tan
Takashi Tani
Ryoko Koike
Keisuke Iwanaga
Mitsuhiro Tsujihata
Osamu Onodera
Ryozo Kuwano
Masatoyo Nishizawa
Akiyoshi Kakita
Takeshi Ikeuchi
Hitoshi Takahashi
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0649-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2010

Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain

Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Aβ42 immunisation in Alzheimer’s disease

TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease

Amyotrophic lateral sclerosis: dash-like accumulation of phosphorylated TDP-43 in somatodendritic and axonal compartments of somatomotor neurons of the lower brainstem and spinal cord

FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration

Pathology and pathogenesis of sensory neuropathy in Friedreich’s ataxia