Beta-Amyloid Imaging for Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disease which affects a person’s memory and ability to learn, reason, communicate and carry out daily activities. Increasing age is the greatest risk factor for AD and there is no prevention or cure. The World Health Organization estimates that Alzheimer’s disease affects over 24,000,000 people worldwide. Currently in the U.S. alone, there are over 5 million Alzheimer’s patients with estimates that by 2050, as many as 16 million Americans could have the disease according to the Alzheimer’s Association. Among the brain changes believed to contribute to the development of Alzheimer’s are the accumulation of the protein beta-amyloid outside nerve cells (neurons) in the brain and the accumulation of the protein tau inside neurons. Approximately 75 to 100 experimental therapies aimed at diagnosing, slowing or stopping the progression of Alzheimer’s are now in human clinical trials.

There is a need for improvements in testing and diagnosis. While there is an accepted diagnostic process for assessing dementia, the only currently definitive diagnosis for AD is a post mortem analysis of brain tissue. A positive finding of plaques and tangles in the brain leads to this definitive diagnosis, clearly much too late to benefit a patient. For this reason, the AD and imaging communities have been united in their search for an effective biomarker of AD which could facilitate earlier definitive diagnosis of AD.

Alzheimer’s disease imaging agents are potentially powerful tools in aiding the diagnosis of AD and evaluation of new drugs aiming to modify amyloid plaque levels and possibly alter disease progression. The prototype agent in this diagnostic quest was identified almost a decade ago at the University of Pittsburgh. This imaging agent targets the deposits of amyloid plaque which are a hallmark of AD pathology. This agent, frequently referred to as Pittsburgh B, or PIB, was a radiolabeled small molecule utilized with Positron Emission Tomography, or PET. As such, the PIB tracer provided strong image resolution and was able to distinguish significant amyloid burdens in the brains of AD patients as opposed to the relative absence of amyloid in subjects without AD. Unfortunately, PIB uses a radio-isotope called C-11, a very short-lived PET isotope, and thus cannot be readily commercialized.

Other PET amyloid tracers are currently moving through the drug development process. These compounds also have the high resolution of PET tracers, but utilize an F-18 isotope, which permits effective broad distribution.

These new second generation agents constitute a major step forward, but each has potential limitations. Navidea’s NAV4694 is undergoing studies aimed at demonstrating several important advantages including clean images with less white matter uptake for identification of lower levels of amyloid and earlier detection; Images that are easier to read and interpret; and Images that can be acquired more quickly.