Globular glial-like inclusions in a patient with advanced Alzheimer’s disease

Abstract

disturbances and memory problems. During disease evolution, apraxia and agnosia completed the clinical picture. He was globally apathetic and presented only occasionally sprouts of aggressiveness, but no prominent behavioural alterations. There were no parkinsonism and no signs of MND. He had no family history of a neurological disorder. He died due to cardiac failure. Unfixed brain weight was 1,305 g. On gross examination, frontal and temporally accentuated brain atrophy with marked ventricular enlargement and severe atrophy of amygdala and hippocampus were observed. Basal ganglia appeared atrophic showing flattening of the head of caudate nucleus (similar to patient 2 of Ahmed’s description). Substantia nigra and locus coeruleus were unremarkable. Histologically, prominent neuronal loss, astrogliosis and microglial proliferation were observed in frontal and temporal cortices, in amygdala, hippocampus and entoand transentorhinal regions. Abundant mature, diffuse and primitive βA4-amyloid plaques (DAKO, Glostrup, Denmark, clone 6F/3D) were detected (Fig. 1a). These were distributed in all cortical areas, basal ganglia, brainstem nuclei and cerebellar cortex, corresponding to a phase 5 according to Thal et al. [6] and to an age-related plaque score C according to CERAD criteria [4]. There was mild, occipitally accentuated leptomeningeal amyloid angiopathy. Furthermore, abundant hyperphosphorylated tau (Thermo-Scientific, clone AT8) immunoreactive neuropil threads, tangles and dystrophic neurites surrounding senile plaques were observed in frontal, temporal (Fig. 1b) and parietal cortex, with no involvement of primary visual cortex. Extensive tau pathology was also detected in insula, cingulum, hippocampus and parahippocampal gyrus, basal ganglia, basal nucleus of Meynert and some brainstem nuclei. In hippocampus, abundant ghost-tangles, neuronal granulovacuolar degeneration and Hirano bodies were also We read with interest the article by Ahmed and colleagues [1] entitled “Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies.” The authors present clinical, neuropathological and biochemical features of two patients, one with frontotemporal dementia (FTD) and the other with motor neuron disease (MND), both sharing the presence of characteristic globular glial 4-repeat tau positive inclusions (oligodendroglial and astrocytic) with different topographical distribution. Previously, Kovacs et al. [3] described in detail seven cases showing FTLD phenotype and abundant white matter globular glial inclusions. Both authors suggest grouping previous terms such as MSTD or FTD-P-MND/PSP-CST, in one encompassing term, as this pathology seems to represent a separate entity among tauopathies. We present the post-mortem neuropathologic study of an 82-year-old man, diagnosed with possible Alzheimer’s disease at the age of 73 years due to progressive word finding