Cell Cycle Re-Entry In Alzheimer's Disease

Main Category: Alzheimer's / Dementia
Also Included In: Neurology / Neuroscience
Article Date: 22 Oct 2008 - 3:00 PDT

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Amyloid plaques are the defining characteristic of Alzheimer's disease (AD), but several studies suggest that soluble amyloid protein is more damaging to neurons. In fact, many signs of neurodegeneration occur before amyloid plaques appear. One such sign is neuronal re-entry into the cell cycle, which occurs in several neurodegenerative diseases. In humans with mild cognitive impairment, DNA replication and expression of cell cycle proteins (e.g., cyclins) appear in brain regions that undergo neurodegeneration in AD. Using transgenic mouse models of AD, Varvel et al. found that cyclins were expressed in frontal cortex many months before plaques appeared, and they were expressed even in mice that never develop plaques. Cyclin expression was prevented by blocking the abnormal processing of amyloid precursor protein that produces amyloid β. Furthermore, amyloid oligomers triggered DNA replication and cyclin expression in primary cortical neurons in vitro, indicating that this early characteristic of degeneration is triggered by soluble amyloid.

Nicholas H. Varvel, Kiran Bhaskar, Anita R. Patil, Sanjay W. Pimplikar, Karl Herrup, and Bruce T. Lamb

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Sara Harris
Society for Neuroscience