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Pathology of SSLOW, a transmissible and fatal synthetic prion protein disorder, and comparison with naturally occurring classical transmissible spongiform encephalopathies
Article first published online: 13 MAR 2014
© 2013 Crown copyright. Neuropathology and Applied Neurobiology © 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 40, Issue 3, pages 296–310, April 2014
How to Cite
Jeffrey, M., McGovern, G., Makarava, N., González, L., Kim, Y.-S., Rohwer, R. G. and Baskakov, I. V. (2014), Pathology of SSLOW, a transmissible and fatal synthetic prion protein disorder, and comparison with naturally occurring classical transmissible spongiform encephalopathies. Neuropathology and Applied Neurobiology, 40: 296–310. doi: 10.1111/nan.12053
- Issue published online: 13 MAR 2014
- Article first published online: 13 MAR 2014
- Accepted manuscript online: 12 APR 2013 03:28AM EST
- Manuscript Accepted: 24 MAR 2013
- Manuscript Received: 1 NOV 2012
- National Institutes of Health (NIH). Grant Number: NS045585
- Veterans Affairs Merit Award
- cerebral amyloid angiopathy;
- membrane pathology;
- prion disease;
- synthetic prion protein;
- transmissible spongiform encephalopathy
Naturally occurring transmissible spongiform encephalopathies (TSEs) accumulate disease-specific forms of prion protein on cell membranes in association with pathognomonic lesions. We wished to determine whether synthetic prion protein disorders recapitulated these and other subcellular TSE-specific changes.
SSLOW is a TSE initiated with refolded synthetic prion protein. Five terminally sick hamsters previously intracerebrally inoculated with third passage SSLOW were examined using light and immunogold electron microscopy.
SSLOW-affected hamsters showed widespread abnormal prion protein (PrPSSLOW) and amyloid plaques. PrPSSLOW accumulated on plasma lemmas of neurites and glia without pathological changes. PrPSSLOW also colocalized with increased coated vesicles and pits, coated spiral membrane invaginations and membrane microfolding. PrPSSLOW was additionally observed in lysosomes of microglial cells but not of neurones or astrocytes.
PrPSSLOW is propagated by cell membrane conversion of normal PrP and lethal disease may be linked to the progressive growth of amyloid plaques. Cell membrane changes present in SSLOW are indistinguishable from those of naturally occurring TSEs. However, some lesions found in SSLOW are absent in natural animal TSEs and vice versa. SSLOW may not entirely recapitulate neuropathological features previously described for natural disease. End-stage neuropathology in SSLOW, particularly the nature and distribution of amyloid plaques may be significantly influenced by the early redistribution of seeds within the inoculum and its recirculation following interstitial, perivascular and other drainage pathways. The way in which seeds are distributed and aggregate into plaques in SSLOW has significant overlap with murine APP overexpressing mice challenged with Aβ.