Sporadic Creutzfeldt–Jakob disease with glial PrP^Res nuclear and perinuclear immunoreactivity

Abstract

Proteinase K-resistant prion protein (PrP ) nuclear and perinuclear immunoreactivity in oligodendrocytes of the frontal cortex is found in one case of otherwise typical sporadic Creutzfeldt-Jakob disease (sCJD) type VV2a. The PrP nature of the inclusions is validated with several anti-PrP antibodies directed to amino acids 130-160 (12F10), 109-112 (3F4), 97-102 (8G8) and the octarepeat region (amino acids 59-89: SAF32). Cellular identification and subcellular localization were evaluated with double- and triple-labeling immunofluorescence and confocal microscopy using antibodies against PrP, glial markers, and histone H3. Based on review of the literature and our own experience, this is a very odd situation that deserves further validation in other cases.

Differential astrocyte and oligodendrocyte vulnerability in murine Creutzfeldt-Jakob disease

“…These findings corroborate the relative resistance of the oligodendrocyte cell line in comparison with the reaction of astrocytes and microglia to PrP SC in a validated model of human CJD. Nevertheless, our results also confirm that oligodendrocytes are vulnerable at advanced stages of murine CJD, as they have previously been noted to be in human sCJD [11][12][13].…”

“…Oligodendrocyte abnormalities may contribute to explain ultrastructural white matter myelin alterations in CJD, and other natural and experimentally induced animal prionopathies [11,[21][22][23]. Moreover, oligodendrocyte alterations described in CJD [11][12][13] and present experimental model may link transition between mild to moderate white matter involvement in common forms compared with severe white matter involvement in panencephalopathic forms of CJD [24][25][26][27][28]. Although alterations of the white matter parallel the intensity of lesions of the grey matter in cases with long duration of the disease [28,29], pioneering panencephalopathic cases, described principally in Japan, were in favour of a primary alteration of the white matter [24,30,31].…”

“…PrP Res immunoreactivity is observed as arrays adjacent to myelinated fibres and as clumps adjacent to oligodendroglial nuclei in the cerebrum and cerebellum in sCJD [ 11 ]. Large, PrP Res -immunoreactive perinuclear and nuclear deposits may occur in oligodendrocytes in a few cases with sCJD [ 12 ]. Morphological observations are complemented by biochemical studies showing reduced expression of a few oligodendrocyte cell markers in the cerebral cortex at the terminal stages of sCJD [ 13 ].…”

Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner

“…The lack of information on this matter invites further inquiry. Rarely, PrPRes can be seen in the nucleus and perinuclear region in oligodendrocytes in CJD (Fernandez-Vega et al, 2018) (Fig. 9).…”

Histotype-Dependent Oligodendroglial PrP Pathology in Sporadic CJD: A Frequent Feature of the M2C “Strain”

“…In contrast, oligodendrocytic PrP pathology has rarely been described. Fernandez-Vega et al [5] reported the presence of nuclear and perinuclear PrP d 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 also observed the presence of oligodendroglial PrP d pathology in the white matter of some sporadic CJD cases.…”