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 beta protein (Abeta) and apoE in Alzheimer's disease (AD) has been clarified, the interaction of prion protein isoform (PrPsc) and apoE in several types of prion diseases (PDs) has not been examined in detail. ApoE colocalization has been confirmed in Congophilic PrPsc 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 PrPsc 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 PrPsc after a conformational change from cellular PrP isoform to PrPsc.

Improvement of neuronal cell survival by astrocyte‐derived exosomes under hypoxic and ischemic conditions depends on prion protein

“…Apolipoprotein E is involved in neural repair and contributes to neuronal survival (Beffert et al, 2006;Gutman et al, 1997;Poirier et al, 1991). Moreover, increased expression of apolipoprotein E and immunohistological co-localization of apolipoprotein E and PrP have been described in animal models of transmissible spongiform encephalopathies (Diedrich et al, 1991;Hochstrasser et al, 1997;Nakamura et al, 2000), suggesting that apolipoprotein E is involved in the pathogenesis of prion diseases. Similarly, enhanced clusterin/apolipoprotein J levels have been found in prion-related encephalopathies.…”

Identification and removal of proteins that co‐purify with infectious prion protein improves the analysis of its secondary structure

“…ApoE transports cholesterol in plasma and in the brain, a critical function known to be perturbed in many neurodegenerative disorders including Alzheimer's disease 53. ApoE is also known to bind various amyloidogenic proteins 54 and has been shown to co‐localize with PrP Sc deposits in vivo 28, 55. Thus, its presence in PrP Sc preparations from prion‐infected brains may simply be due to its ability to bind PrP Sc .…”

“…ApoE is also known to bind various amyloidogenic proteins [54] and has been shown to co-localize with PrP Sc deposits in vivo [28,55]. Thus, its presence in PrP Sc preparations from prion-infected brains may simply be due to its ability to bind PrP Sc .…”

The 129 codon polymorphism of the Prion Protein gene influences earlier cognitive performance in Down syndrome subjects

“…In prion diseases apoE binds to prion amyloid plaques and its phenotype plays an important role in the amyloid genesis process and acceleration of the PrP aggregation [14,18]. It has been suggested that ApoE4, when combined with valine at codon 129, may increase the total amount of prion protein deposited in plaque form.…”