Abstract
In sporadic Creutzfeldt-Jakob disease, molecular subtypes are neuropathologically well identified by the lesioning profile and the immunohistochemical PrPd deposition pattern in the grey matter (histotypes). While astrocytic PrP pathology has been reported in variant CJD and some less frequent histotypes (e.g., MV2K), oligodendroglial pathology has been rarely addressed. We assessed a series of sCJD cases with the aim to identify particular histotypes that could be more prone to harbor oligodendroglial PrPd. Particularly, the MM2C phenotype, in both its more “pure” and its mixed MM1+2C or MV2K+2C forms, showed more frequent oligodendroglial PrP pathology in the underlying white matter than the more common MM1/MV1 and VV2 histotypes, and was more abundant in patients with a longer disease duration. We concluded that the MM2C strain was particularly prone to accumulate PrPd in white matter oligodendrocytes.
Highlights
Attention has been mainly focused on neuronal dysfunction, as PrPc is enriched in synapses and its pathology positively correlates with the neurodegenerative process and clinical symptoms [1]
The oligodendroglial pathology was evident in cases with extensive patchy-perivacuolar PrP deposits in the overlying cortex (Figure 1H,I)
Oligodendroglial PrPd deposits were comparable with coiled bodies observed in the four-repeat tauopathies, such as progressive supranuclear palsy, corticobasal degeneration or argyrophilic grain disease, or even glial cytoplasmic alphasynuclein inclusions of MSA, as some PrPd aggregates appeared coarser or microglobular
Summary
Attention has been mainly focused on neuronal dysfunction, as PrPc is enriched in synapses and its pathology positively correlates with the neurodegenerative process and clinical symptoms [1]. The deposition of disease-associated PrP (PrPd) has been described in astrocytes [3], in MV2K cases [4]. Oligodendrocytic PrP pathology has rarely been described. Fernandez-Vega et al [5] reported the presence of nuclear and perinuclear PrPd in oligodendrocytes in the frontal white matter in a 66-year-old man with an otherwise classical VV2-histotype, who had a disease duration of 4,5 months. We observed the presence of oligodendroglial PrPd pathology in the white matter of some sporadic CJD cases. This finding prompted us to analyze in more detail whether some specific CJD histotypes might be more prone to accumulate PrPd in this particular glial cell type
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