Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies

Acta Neuropathol. 2011 Oct;122(4):415-28. doi: 10.1007/s00401-011-0857-4. Epub 2011 Jul 21.

Abstract

A number of recent studies have described cases with tau-positive globular oligodendroglial inclusions (GOIs) and such cases have overlapping pathological features with progressive supranuclear palsy (PSP), but present with clinical features of motor neuron disease (MND) and/or frontotemporal dementia (FTD). These two clinical phenotypes have been published independently and as a result, have come to be considered as distinct disease entities. We describe the clinicopathological and biochemical features of two cases with GOIs: one with clinical symptoms suggestive of MND and the other with FTD. Histological changes in our two cases were consistent with their clinical symptoms; the MND case had severe neurodegeneration in the primary motor cortex and corticospinal tract, whereas the FTD case had severe involvement of the frontotemporal cortices and associated white matter. Immunohistochemistry in both cases revealed significant 4-repeat (4R) tau pathology primarily in the form of GOIs, but also in astrocytes and neurons. Astrocytic tau pathology was morphologically similar to that seen in PSP, but in contrast was consistently negative for Gallyas silver staining. Tau-specific western blotting revealed 68, 64 and 35 kDa bands, showing further overlap with PSP. The underlying neuropathological features of these two cases were similar, with the major difference relating to the regional distribution of pathology and resulting clinical symptoms and signs. The globular nature of glial inclusions and the non-fibrillar properties of tau in astrocytes are characteristic features that allow them to be distinguished from PSP and other tauopathies. We, therefore, propose the term globular glial tauopathy as an encompassing term to classify this emerging class of 4R tauopathy.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diagnosis, Differential
  • Fatal Outcome
  • Female
  • Frontotemporal Dementia / diagnosis*
  • Frontotemporal Dementia / genetics
  • Frontotemporal Dementia / pathology*
  • Humans
  • Male
  • Motor Neuron Disease / diagnosis*
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / pathology*
  • Oligodendroglia / pathology*
  • Tauopathies / diagnosis*
  • Tauopathies / genetics
  • Tauopathies / pathology*
  • Trinucleotide Repeat Expansion / genetics*