In variant Creutzfeldt-Jakob disease (vCJD), cortical deposition of abnormal prion protein (PrP) aggregates as florid amyloid plaques occur.1 The 9.4T MRI resolves horizontal laminations of the isocortex.2 We scanned blocks of postmortem vCJD brain and a sporadic CJD control after passive staining with gadodiamide using a high-resolution 3D gradient echo sequence. Distinct hypointense foci on the MRI in vCJD (figure, A and C) but not control (figure, B) corresponded to PrP-amyloid plaques with greatest density in the central layers of the cortex on histology (figure, D–G). As human high-field systems become widespread, noninvasive monitoring of PrP-amyloid plaques may be of utility in future treatment trials.
Figure. 9.4T MRI of the postmortem human brain and corresponding histology.
High-resolution (58 mm isotropic voxels) 3D gradient echo sequence (relaxation time = 20 ms, echo time = 5 ms, field of view 30 × 30 mm2, matrix 512 × 512, 16 averages) (A, B) and magnified view (C) with corresponding immunohistochemically stained section (D–G). Scale bar: 3 mm (D) and 200 µm (E–G). sCJD = sporadic Creutzfeldt-Jakob disease; vCJD = variant Creutzfeldt-Jakob disease.
Footnotes
Author contributions: Harpreet Hyare: experimental design. Po Wah So: experimental design. Sebastian Brandner: interpretation of histologic material, pathologic-radiologic correlation. John Collinge: drafting/revising the manuscript, funding of the study. Harold Parkes: MRI scanning.
Study funding: This work was supported by the UK Medical Research Council. Some of this work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the National Institute for Health Research Comprehensive Biomedical Research Centres funding scheme.
Disclosure: Prof. John Collinge serves on the editorial boards of Neurobiology of Disease, Journal of Neurobiology, Neurogenetics and Neurodegenerative Disease Management; is a director and shareholder of D-Gen Ltd., an academic spin-out company working in the field of prion disease diagnosis, decontamination, and therapeutics; and receives research support from the UK Medical Research Council, the National Institute for Health Research (England), and the Wolfson Foundation. Go to Neurology.org for full disclosures.
References
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