Acta Neuropathologica

, Volume 126, Issue 4, pp 537–544 | Cite as

Globular glial tauopathies (GGT): consensus recommendations

  • Zeshan Ahmed
  • Eileen H. Bigio
  • Herbert Budka
  • Dennis W. Dickson
  • Isidro Ferrer
  • Bernardino Ghetti
  • Giorgio Giaccone
  • Kimmo J. Hatanpaa
  • Janice L. Holton
  • Keith A. Josephs
  • James Powers
  • Salvatore Spina
  • Hitoshi Takahashi
  • Charles L. WhiteIII
  • Tamas Revesz
  • Gabor G. Kovacs
Consensus Paper

Abstract

Recent studies have highlighted a group of 4-repeat (4R) tauopathies that are characterised neuropathologically by widespread, globular glial inclusions (GGIs). Tau immunohistochemistry reveals 4R immunoreactive globular oligodendroglial and astrocytic inclusions and the latter are predominantly negative for Gallyas silver staining. These cases are associated with a range of clinical presentations, which correlate with the severity and distribution of underlying tau pathology and neurodegeneration. Their heterogeneous clinicopathological features combined with their rarity and under-recognition have led to cases characterised by GGIs being described in the literature using various and redundant terminologies. In this report, a group of neuropathologists form a consensus on the terminology and classification of cases with GGIs. After studying microscopic images from previously reported cases with suspected GGIs (n = 22), this panel of neuropathologists with extensive experience in the diagnosis of neurodegenerative diseases and a documented record of previous experience with at least one case with GGIs, agreed that (1) GGIs were present in all the cases reviewed; (2) the morphology of globular astrocytic inclusions was different to tufted astrocytes and finally that (3) the cases represented a number of different neuropathological subtypes. They also agreed that the different morphological subtypes are likely to be part of a spectrum of a distinct disease entity, for which they recommend that the overarching term globular glial tauopathy (GGT) should be used. Type I cases typically present with frontotemporal dementia, which correlates with the fronto-temporal distribution of pathology. Type II cases are characterised by pyramidal features reflecting motor cortex involvement and corticospinal tract degeneration. Type III cases can present with a combination of frontotemporal dementia and motor neuron disease with fronto-temporal cortex, motor cortex and corticospinal tract being severely affected. Extrapyramidal features can be present in Type II and III cases and significant degeneration of the white matter is a feature of all GGT subtypes. Improved detection and classification will be necessary for the establishment of neuropathological and clinical diagnostic research criteria in the future.

Supplementary material

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Supplementary material 1 (DOCX 12 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Zeshan Ahmed
    • 1
  • Eileen H. Bigio
    • 2
  • Herbert Budka
    • 3
    • 12
  • Dennis W. Dickson
    • 4
  • Isidro Ferrer
    • 5
  • Bernardino Ghetti
    • 6
  • Giorgio Giaccone
    • 7
  • Kimmo J. Hatanpaa
    • 8
  • Janice L. Holton
    • 1
  • Keith A. Josephs
    • 9
  • James Powers
    • 10
  • Salvatore Spina
    • 6
  • Hitoshi Takahashi
    • 11
  • Charles L. WhiteIII
    • 8
  • Tamas Revesz
    • 1
  • Gabor G. Kovacs
    • 3
  1. 1.Department of Molecular Neuroscience, Queen Square Brain Bank Institute of Neurology, University College LondonLondonUK
  2. 2.Department of Pathology, Northwestern Alzheimer Disease CenterNorthwestern Feinberg School of MedicineChicagoUSA
  3. 3.Institute of NeurologyMedical University of ViennaViennaAustria
  4. 4.Mayo ClinicJacksonvilleUSA
  5. 5.Institute of NeuropathologyUniversity Hospital Bellvitge, University of Barcelona, CIBERNEDHospitalet de LLobregatSpain
  6. 6.Department of Pathology and Laboratory Medicine, Indiana Alzheimer Disease CenterIndiana University School of MedicineIndianapolisUSA
  7. 7.Fondazione IRCCS Istituto Neurologico Carlo BestaMilanItaly
  8. 8.Department of Pathology, Alzheimer’s Disease CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  9. 9.Mayo ClinicRochesterUSA
  10. 10.University of RochesterSchool of Medicine and DentistryRochesterUSA
  11. 11.Department of Pathology, Brain Research InstituteNiigata UniversityNiigataJapan
  12. 12.Institute of NeuropathologyUniversity Hospital ZurichZurichSwitzerland

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