Immunohistochemical Detection of Receptor-Associated Protein in Normal Human Brain and Alzheimer's Disease

John Provias,Brian Jeynes

doi:10.4061/2010/173496

Abstract

This study is one of the few to characterize immunohistochemically the distribution and localization of Receptor-Associated Protein (RAP) in human autopsy brain. The results show prominent cortical neuronal localization. RAP is clearly identified in large neuronal dendritic/axonal processes. RAP is expressed in both large pyramidal and smaller interneurons. Occasional, much less frequent RAP is detectable in glial cells in white matter, which appear to be predominantly astrocytic. Although RAP is detectable immunohistochemically in Alzheimer's disease autopsy brain, the level of expression appears significantly reduced relative to age-matched control brains. These results suggest, at the immunohistochemical level, that there is a reduction of RAP protein in Alzheimer's disease brain (cortex). In terms of Alzheimer's disease pathophysiology, a reduction of neuronal RAP could then lead to reduced membrane expression of LRP, since RAP has also been shown to be an LRP antagonist.

Highlights

Receptor-associated protein (RAP) is a 39-kilo Dalton protein which is part of the large family of small GTPase proteins
Our results indicate that RAP can be detected immunohistochemically in autopsy human brain (Figure 1)
This study has demonstrated the immunohistochemical detection of RAP in both normal and Alzheimer’s disease human cortex

Summary

Introduction

Receptor-associated protein (RAP) is a 39-kilo Dalton protein which is part of the large family of small GTPase proteins. Alzheimer’s disease is characterized by the excessive accumulations of beta amyloid peptide within brain regions, including areas of cortex. Given that RAP can modulate LRP function; it potentially could play a role in the transmembrane intracellular handling of APP and subsequent conversion to beta amyloid peptide. This clearly could be significant in terms of contributing to AD pathogenesis by affecting the beta amyloid peptide burden. There are a number of lines of evidence suggesting a reduction of beta amyloid peptide clearance contributing to the accumulations which occur in Alzheimer’s disease [11]. Any factor which alters or modulates beta amyloid uptake and neuronal processing, or microvascular clearance through modulations of other receptor proteins such as LRP, could

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Conclusion