Nonisotopic in situ hybridization of amyloid beta protein precursor in Alzheimer's disease: expression in neurofibrillary tangle bearing neurons and in the microenvironment surrounding senile plaques

Abstract

We have used nonisotopic in situ hybridization techniques with biotinylated junctional oligonucleotide probes to study expression of amyloid precursor protein (APP) 695 and 751 mRNA in the hippocampal formation of Alzheimer's disease. Both mRNAs are strongly expressed in neurons of the hippocampal formation, particularly in the dentate gyrus granule cells and the pyramidal neurons of CA3. The patterns of expression of neither APP695 nor APP751 mRNA correlate well with the stereotyped topography of neurofibrillary tangles or senile plaques, which occur primarily in CA1 and subiculum. We double-labeled in situ sections with immunohistochemical reagents for neurofibrillary tangles or senile plaques. Neurons that contain neurofibrillary tangles continue to express APP mRNA. The level of APP695 and APP751 was measured semiquantitatively by optical density measurements in neurons that were close to (within 25 μm) or farther from a senile plaque (more than 100 μm). There was no increase in expression in neurons in the immediate microenvironment of senile plaques. Our results suggest that no major change in distribution or type of APP mRNA accompanies neurofibrillary tangle or senile plaque development.