Support for the Amyloid Hypothesis

Contributed by: Dennis Fortier, President, Medical Care Corporation
________________________________________________

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.

Neuro-Imaging and Alzheimer's: The Basics

Contributed by: Dennis Fortier, President, Medical Care Corporation
________________________________________________

Rarely a day goes by when I do not see several news items about the role of neuro-imaging in detecting, treating, or monitoring the progression of Alzheimer's disease. Here are a few comments to bear in mind as you consume the daily press.

Magnetic Resonance Imaging (MRI) yields an image of brain structure and will reveal tumors, strokes, and (importantly for Alzheimer's disease) atrophy (or shrinkage) in particular parts of the brain that can be helpful in reaching an accurate diagnosis.

Positron Emission Tomography (PET) yields an image of brain metabolism and reveals where brain cells are engaged the healthy activities of their daily function. In some instances, this can reveal an earlier stage of a problem than MRI would reveal because cells may have stopped functioning but remained intact structurally.

Many news stories report on "tracers" or agents such as PIB that, once injected into the blood, make their way to the brain and bind with the beta amyloid, rendering it clearly visible in the scan. This is important because many scientists believe beta amyloid accumulation may be the cause of Alzheimer's disease.

While the PET/PIB studies are generally promising, public optimism should be tempered by the fact that the PIB compound has some significant practical shortcomings. It decays rapidly and must be injected very quickly after being manufactured. For that reason alone, the prospect of wide-spread use in a clinical setting is a distant one.