Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain.

Abstract	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.
Authors	J Busser, D S Geldmacher, K Herrup
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 18 Issue 8 Pg. 2801-7 (Apr 15 1998) ISSN: 0270-6474 [Print] United States
PMID	9525997 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Biomarkers CCNB1 protein, human Cell Cycle Proteins Cyclin B Cyclin B1 Cyclin D Cyclins Proliferating Cell Nuclear Antigen Proto-Oncogene Proteins CDK4 protein, human Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases
Topics	Aged Aged, 80 and over Alzheimer Disease (metabolism) Biomarkers Brain Stem (chemistry, cytology) Cell Cycle Proteins (physiology) Cell Death (physiology) Cyclin B (analysis, metabolism) Cyclin B1 Cyclin D Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases (analysis, metabolism) Cyclins (analysis, metabolism) Female Hippocampus (chemistry, cytology) Humans Male Middle Aged Neurons (chemistry, cytology, metabolism) Proliferating Cell Nuclear Antigen (analysis, metabolism) Proto-Oncogene Proteins

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