[Frontiers in Bioscience 7, a44-49, April 1, 2002]

SIGNIFICANCE OF INTRACELLULAR Ab42 ACCUMULATION IN ALZHEIMER'S DISEASE

T. Tabira 1, D. H. Chui 2, and S. Kuroda 3

1 National Institute for Longevity Sciences, Obu, Aichi 474-8522, 2 Laboratory for Alzheimer Disease, Riken Brain Science Institute, Wako, Saitama 351-0198, and 3 Department of Neuropsychiatry, Okayama University Medical School, Okayama 700-8558, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods
3.1. PS1 transgenic mice and tissue processing
3.2. Human brain studies
4. Results
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

Ab plays a pivotal role in the pathogenesis of Alzheimer's disease (AD), but it is still obscure how it causes AD. We have established transgenic mice carrying wild-type or familial Alzheimer's disease (FAD) mutant-type presenilin 1 (PS1). In these mice, the number of cortical and hippocampal neurons decreased along with age in mutant mice. In addition, the old mutant mice showed a significant increase of dark neurons by silver staining and the number of neurons with intracellular Ab 42 by immunohistochemistry. Our extended study also showed a significant increase of intracellular Ab 42-positive neurons in isolated cases of AD as well as in PS1 mutant FAD cases. These neurons frequently showed apoptotic staining. However, coincidence of apoptotic markers and intraneuronal neurofibrillary tangles (NFT) was insignificant. Notably intraneuronal Ab 42-labeling was frequently seen in a case of AD showing cotton-wool type senile plaques with a few NFT positive neurons and dystrophic neurites. These results indicate that intraneuronal deposition of Ab 42 is important in the pathogenesis of AD.