[Frontiers in Bioscience E4, 2101-2109, January 1, 2012]

The contributions of unscheduled neuronal cell cycle events to the death of neurons in Alzheimer's disease

Karl Herrup1

1Dept. of Cell Biology and Neuroscience, Nelson Biological Laboratories, 604 Allison Road, Piscataway, NJ 0854

TABLE OF CONTENTS

1. Abstract
2. Background
2.1. The strange linkage between cell death and cell cycle regulation
2.2. Cell death in Alzheimer's disease - general considerations
2.3. Cell death in Alzheimer's disease - the involvement of cell cycle processes
2.4. CRND in Alzheimer's disease mouse models
2.5. The R1.40 model accurately predicts cerebellar involvement in AD
3. Concluding comments
4. References

1. ABSTRACT

Alzheimer's disease is a neurodegenerative disorder that accounts for the majority of the dementia in individuals over the age of 65. While much has been learned about the biology and biochemistry of the tau tangles and beta-amyloid plaques, less is known about the cell biology of the neuronal cell death process. This review examines one feature of this process, the unexpected occurrence of unscheduled cell cycle events in mature and normally non-mitotic neurons in the at-risk neuronal populations. The correlation of neuronal cell cycling and cell death is not unique to Alzheimer's, but the evidence in both human Alzheimer's disease and its mouse models suggests that these events are early disease related processes, that they are driving forces of the disease rather than indirect symptoms. Defining the biochemistry behind cell cycle initiation holds promise as a fresh therapeutic approach in the battle against this devastating disease.