An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex

Abstract

Globular glial tauopathy (GGT) is a 4-repeat (4R) tauopathy in which 4R tau accumulates to form globular glial inclusions (GGIs), predominantly in oligodendroglia. To date, little has been reported on iron deposits in patients with GGT. We report a case of GGT with iron deposits in a 78-year-old woman presenting with an 8-year history of slowly progressing limb weakness and cognitive decline. Susceptibility-weighted imaging revealed a low signal intensity in the right precentral gyrus, suggesting iron deposition. A clinical diagnosis of motor neuron disease with dementia was made 4 years after onset. At autopsy, gross pathological findings showed atrophy of the frontal and temporal lobes. A localized area of the precentral gyrus corresponding to the most severely affected limb showed the strongest atrophy, macroscopically, and displayed 4R tau-immunoreactive GGIs and microscopically many ferritin-immunoreactive neurons. We diagnosed this patient as having GGT. This is the first GGT case with iron deposition confirmed both radiologically and pathologically.

Globular glial tauopathy Type II: Clinicopathological study of two autopsy cases

“…From a neuropathological viewpoint, the present two cases demonstrated predominant occurrence of tau‐positive oligodendrocytic inclusions, including GOIs, CBs and NTs, in the affected gray and white matter, strongly suggesting that the two patients had suffered from GGT Type II . In case 1, the electron microscopic and biochemical findings were also in agreement with a diagnosis of Type II . With regard to the neuropathology in Type III, predominant occurrence of GAIs in the affected gray matter is a feature .…”

“…Immunoblot analysis using non‐dephosphorylated samples revealed cleaved low molecular‐mass tau fragments of approximately ~35 kDa (Fig. ), being similar to PSP tau . There were no mutations in the MAPT gene.…”

“…It has been reported that, unlike PSP, although the tau pathology is not severe, it is also present in the subcortical nuclei and brainstem in cases of 4R tauopathy, and this is now recognized to be an example of GGT Type II . Recently, an autopsy case of GGT showing clinical features of MND and dementia has been reported, in which the GGIs (mainly GOIs) were densely distributed at the gray‐white matter junction in the frontal and temporal lobes, including the precentral gyrus . Based on the tau pathology, the patient was considered to have GGT Type II …”

“…1 After publication of the 2013 consensus recommendation, 1 a number of additional cases were reported. [3][4][5][6][7] However, even at present, the number of reported GGT cases remains too small to allow discussion of the clinical/neuropathological correlations in the 4R tauopathies. We report here the clinical and neuropathological findings in two GGT cases and compare them with those of previously described cases.…”

“…After publication of the 2013 consensus recommendation, a number of additional cases were reported . However, even at present, the number of reported GGT cases remains too small to allow discussion of the clinical/neuropathological correlations in the 4R tauopathies.…”