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Next Article 
The Journal of Neuroscience, April 15, 1998, 18(8):2801-2807
Ectopic Cell Cycle Proteins Predict the Sites of Neuronal Cell
Death in Alzheimer's Disease Brain
Jonathan
Busser,
David S.
Geldmacher, and
Karl
Herrup
Alzheimer Research Laboratory, Department of Neurology, Case
Western Reserve University, School of Medicine, Cleveland, Ohio 44106
Alzheimer's disease (AD) is a major dementing illness
characterized by regional concentrations of senile plaques,
neurofibrillary tangles, and extensive neuronal cell death. Although
cell and synaptic loss is most directly linked to the severity of
symptoms, the mechanisms leading to the neuronal death remain unclear.
Based on evidence linking neuronal death during development to
unexpected reappearance of cell cycle events, we investigated the
brains of 12 neuropathologically verified cases of Alzheimer's disease and eight age-matched, disease-free controls for the presence of cell
cycle proteins. Aberrant expression of cyclin D, cdk4, proliferating
cell nuclear antigen, and cyclin B1 were identified in the hippocampus,
subiculum, locus coeruleus, and dorsal raphe nuclei, but not
inferotemporal cortex or cerebellum of AD cases. With only one
exception, control subjects showed no significant expression of cell
cycle markers in any of the six regions. We propose that
disregulation of various components of the cell cycle is a
significant contributor to regionally specific neuronal death in
AD.
Key words:
Alzheimer's disease; cell death; cyclin D; cyclin B1; PCNA; cdk4
Copyright © 1998 Society for Neuroscience 0270-6474/98/1882801-07$05.00/0
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