For unknown reasons, nerve cells (neurons) affected by AD and many other neurodegenerative diseases often start to divide before they die. The new study shows that, in animal models of AD, this abnormal cell division starts long before amyloid plaques or other markers of the disease appear. Cell division occurs through a process called the cell cycle. "If you could stop cell cycling, you might be able to stop neurons from dying prematurely. This could be a fresh approach to therapy for Alzheimer's and other diseases, including stroke, amyotrophic lateral sclerosis [also known as Lou Gehrig's disease], and HIV dementia," says Karl Herrup, Ph.D., of Case Western Reserve University in Cleveland, who led the study.
The researchers compared the brains of three different mouse models of AD to brains from normal mice, looking specifically for markers of cell cycling. They found that, in the AD mouse models, cell cycle-related proteins appeared in neurons 6 months before the first amyloid plaques or disease-related immune reactions developed in the brain. Many of the neurons also had increased numbers of chromosomes, which is typical of cells that have begun to divide. These changes were not seen in normal mice. The regions of the brain most affected by the neuronal cell cycling were the cortex and the hippocampus the same regions most affected in AD. The cortex is important for thought and reasoning, while the hippocampus plays a key role in learning and memory. Some parts of the brainstem also showed evidence
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NIH/National Institute of Neurological Disorders and Stroke