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Rolipram - a potential new treatment for Alzheimer disease

JCI Journals

Alzheimer disease (AD) is the most common form of dementia in the elderly and classic clinical features include memory loss, deterioration in speech, and behavioral disturbances. Doctors increasingly concede that central to the cause of AD is the production and accumulation of beta-amyloid (Ab), which is toxic in the brain. There are only a few clinical therapeutic options for AD patients but in the December 1 issue of the Journal of Clinical Investigation, Ottavio Arancio, Michael Shelanksi, and colleagues from Columbia University, New York, propose a new treatment to counter AD-associated memory loss.

The authors show that brief treatment of a mouse model of AD with a phosphodiesterase 4 inhibitor, rolipram, improves memory in both long-term potential and contextual learning - both measurements of brain function.

Rolipram's protective effect is due to its ability to modify gene expression, making brain synapses more resistant to the insult caused by the accumulation of Ab. The beneficial effect of rolipram treatment was found to extend for at least 2 months after the end of one course of the treatment. The authors also found that the beneficial effects of treatment were not limited to early stages of the disease when behavioral changes were initially noted and were actually greater in older mice, suggesting that this class of drug might not be limited to treatment in the initial phases of disease.

Further studies will determine how long improvements in cognitive function persist after a single course of treatment and whether better or more long-lasting results can be achieved with either continuous treatment or successive courses of treatment. This study suggests that drugs, such as rolipram, the inhibit phosphodiesterase have the potential to prevent the memory loss characteristic of Alzheimer disease.


TITLE: Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment

Ottavio Arancio or Michael Shelanski
Department of Pathology
Columbia University
New York, New York, USA
Phone: 212-342-5527 or 212-305-3300
Fax: 212-342-5524 or 212-305-5498
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