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Non‐amyloid and amyloid prion protein deposits in prion‐infected mice differ in blockage of interstitial brain fluid
Author(s) -
Rangel A.,
Race B.,
Striebel J.,
Chesebro B.
Publication year - 2013
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2012.01303.x
Subject(s) - scrapie , amyloid (mycology) , interstitial fluid , genetically modified mouse , amyloidosis , chronic wasting disease , pathology , chemistry , cerebral amyloid angiopathy , biology , prion protein , transgene , medicine , biochemistry , disease , dementia , gene
Aims Prion diseases are characterized by brain deposits of misfolded aggregated protease‐resistant prion protein ( PrP ), termed PrPres . In humans and animals, PrPres is found as either disorganized non‐amyloid aggregates or organized amyloid fibrils. Both PrPres forms are found in extracellular spaces of the brain. Thus, both might block drainage of brain interstitial fluid ( ISF ). The present experiments studied whether ISF blockage occurred during amyloid and/or non‐amyloid prion diseases. Methods Various‐sized fluorescein‐labelled ISF tracers were stereotactically inoculated into the striatum of adult mice. At times from 5 min to 77 h, uninfected and scrapie‐infected mice were compared. C57BL /10 mice expressing wild‐type anchored PrP , which develop non‐amyloid PrPres similar to humans with sporadic C reutzfeldt– J akob disease, were compared with Tg 44+/+ mice (transgenic mice secreting anchorless PrP ) expressing anchorless PrP , which develop amyloid PrPres similar to certain human familial prion diseases. Results In C57BL /10 mice, extensive non‐amyloid PrPres aggregate deposition was not associated with abnormal clearance kinetics of tracers. In contrast, scrapie‐infected Tg 44+/+ mice showed blockage of tracer clearance and colocalization of tracer with perivascular PrPres amyloid. Conclusions As tracer localization and clearance was normal in infected C57BL /10 mice, ISF blockage was not an important pathogenic mechanism in this model. Therefore, ISF blockage is unlikely to be a problem in non‐amyloid human prion diseases such as sporadic C reutzfeldt– J akob disease. In contrast, partial ISF blockage appeared to be a possible pathogenic mechanism in Tg 44+/+ mice. Thus this mechanism might also influence human amyloid prion diseases where expression of anchorless or mutated PrP results in perivascular amyloid PrPres deposition and cerebral amyloid angiopathy.