Consistent immunohistochemical detection of intracellular beta-amyloid42 in pyramidal neurons of Alzheimer's disease entorhinal cortex

Abstract

We compared the effects of three pretreatment immunohistochemical techniques (no pretreatment, pepsin predigestion and heat pretreatment (HEAT)) for detecting intracellular beta-amyloid42 (Abeta42) in pyramidal neurons of formalin-fixed Alzheimer's disease (AD) cortices (n = 25). Although all three protocols immunostained Abeta42 in amyloid plaques using four commercially-obtained Abeta42 specific antibodies, only the HEAT protocol consistently detected prominent intracellular Abeta42 in pyramidal neurons. This suggests that the Abeta42 present in amyloid plaques may be structurally distinct from that located within the neurons perhaps due to differential binding proteins coupling or a consequence of formalin fixation. Detection of an abundant intracellular Abeta42 in neurons may provide alternate explanations for the origin of dense-core amyloid plaques in AD cortices other than the conventional chronic extracellular Abeta42 deposition hypothesis.