Study links Alzheimer’s disease to abnormal cell division

While technology has made strides in imaging amyloid plaques associated with Alzheimer's disease, a debate continues whether the plaques are the cause or the result of the disease. A new study suggests the latter.

Karl Herrup, Ph.D., and colleagues at Case Western Reserve University in Cleveland found through studying mice that AD may be triggered when adult neurons try to divide.

For unknown reasons, neurons affected by AD and many other neurodegenerative diseases often start to divide before they die. The new study shows that this abnormal cell division - called cell cycling - starts long before amyloid plaques or other markers of the disease appear (J Neurosci 2006;26:775-784).

"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, and HIV dementia," said Herrup, director of the Alzheimer's Disease Center at Case Western.

Researchers found that cell cycle-related proteins appeared in neurons six 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 neuronal cell cycling were the cortex and the hippocampus, the same regions most affected in AD. Some parts of the brain stem also showed evidence of cell cycling.

While the cell cycling appeared to be necessary for neurons to die, it was not an immediate cause of cell death. Instead, the affected neurons appeared to live for many months in a near-functional state, with the mice showing only mild behavioral changes during that time. This suggests that another type of cellular problem, still unidentified, must damage the neurons in order for them to die, Herrup said.

The findings shed new light on the theory that the accumulation of amyloid beta in the brain causes the neuron death in AD. Because the abnormal cell cycling begins months before the formation of amyloid plaques, it is unlikely that the plaques themselves trigger the disease process, according to the study.

However, tiny clumps made up of several amyloid beta molecules (called micromolecular aggregates) form before the plaques and may trigger the disease.

Researchers are now trying to determine if the anti-inflammatory drug ibuprofen can stop abnormal cell cycling in neurons and halt neurodegeneration.

For more information from the Diagnostic Imaging archives:

Amyloid imaging and spinal fluid protein help diagnose Alzheimer's disease

MRI-detected brain atrophy predicts dementia

Computer programs aid Alzheimer's diagnosis

Amyloid plaques hasten progress of dementia