Distribution of amyloid β protein precursor in the Alzheimer's disease brain

Abstract

In order to clarify the distribution and pathological changes of the amyloid β protein precursor (βAPP), 10 Alzheimer's disease (AD) brains and seven normal control brains were examined by immunocytochemistry and in situ hybridization histochemistry. All βAPP isoforms were distributed evenly in neuronal cell bodies and their axons and dendrites. The βAPP-positive neuronal processes showed mesh-like networks. In AD brains, βAPP-positive neurons and mesh-like networks were generally decreased in spite of some intensely labeled neurons. All βAPP isoforms accumulated in neuronal processes, dystrophic neurites and senile plaques. In situ hybridization histochemistry confirmed that all isoforms of βAPP were expressed in neurons in control brains. In AD brains, the βAPP mRNA signal was generally decreased besides some intense signal neurons corresponding to immunostaining findings. Few astrocytes expressed βAPP. Thus, uniform expression and distribution of βAPP were disturbed in AD brains showing uneven decreases or increases of neuronal βAPP expression in individual neurons and βAPP accumulation in neurons, neuronal processes and abnormal structures including dystrophic neurites, senile plaques and neurofibrillary tangles.