Immunohistochemical detection of apolipoprotein E within prion-associated lesions in squirrel monkey brains

Abstract

The interaction of various amyloid precursors and apolipoprotein E (apoE) is important for Congophilic amyloid formation. As for cerebral amyloidoses, although the correlation between amyloid β protein (Aβ) and apoE in Alzheimer’s disease (AD) has been clarified, the interaction of prion protein isoform (PrP^sc) and apoE in several types of prion diseases (PDs) has not been examined in detail. ApoE colocalization has been confirmed in Congophilic PrP^sc plaques, but to clarify the participation of apoE in the early stage of PDs, apoE deposition in immature lesions without Congophilic amyloid in PDs needs to be examined. In the present study two squirrel monkeys were inoculated with mouse PrP^sc derived from sheep scrapie, and showed signs of severe spongiform degeneration. These lesions were immunohistochemically characterized as patchy perivacuolar and diffuse synaptic lesions without Congophilic amyloid. The central portion of the assemblies involving a few patchy perivacuolar lesions was detected by methenamine silver staining and appeared as a plaque-like lesion. ApoE was colocalized in all the plaque-like lesions and in half of the patchy perivacuolar lesions, but not in any diffuse synaptic lesions. These immunohistochemical characteristics indicated that apoE colocalization occurred in moderate mature lesions in PDs, and apoE might play an important role in the aggregation of PrP^sc after a conformational change from cellular PrP isoform to PrP^sc.