Support for the Amyloid Hypothesis

Contributed by: Dennis Fortier, President, Medical Care Corporation
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A prevalent theory explaining the cause of Alzheimer's disease is that amyloid deposits accumulate in the brain and disrupt cell function.

While this hypothesis has driven the majority of drug development efforts over the past three years, the theory has some apparent weaknesses that must be explained. Specifically, researchers have not been able to explain why some adults with extensive amyloid deposits do not have Alzheimer's disease.

A study out of UCSF and published in Behavioral Neurology lends some support to the amyloid hypothesis. The authors reviewed over 100 published studies that involved PET scans and the PIB compound and found that there is a strong correlation between amyloid load in the brain and cognitive decline due to Alzheimer's disease. Importantly, they have documented support for the notion that there is a time lag between amyloid build-up and cognitive decline.

"Amyloid deposits appear to reach a plateau early in the disease course, when patients experience very mild symptoms or no symptoms at all," says Rabinovici, a recipient of new investigator awards from the Alzheimer's Association and the National Institute on Aging. "By the time patients have developed the symptoms of Alzheimer's disease, clinical decline and brain changes are occurring independently of further amyloid accumulation. This suggests that we have been starting treatment too late, and that amyloid-based therapies are most likely to work very early in the disease process."

Gaining a deeper understanding of the progressive pathology of Alzheimer's disease will be critical in developing effective treatment. In the meantime, the body of evidence supporting earlier intervention continues to grow.