What Causes Alzheimer's? Researchers Tie Beta-amyloids To Brain Dysfunction

"Our findings show that beta-amyloid is associated with brain dysfunction--even in apparently normal elderly individuals--providing further evidence that it is likely related to the fundamental cause of Alzheimer's disease," said Christopher Rowe, director of the nuclear medicine department and Centre for PET at Austin Hospital in Melbourne, Victoria, Australia.

Additionally, in using agent PIB (Pittsburgh Compound B) and positron emission tomography (PET), researchers "demonstrated that PIB PET is able to detect the early pathological changes of Alzheimer's disease long before the development of dementia," he indicated. "Trials of anti-amyloid drugs are underway. If these prove successful, amyloid imaging will have a vital role in identifying those in need of treatment to prevent the development of Alzheimer's dementia," added Rowe.

Alzheimer's disease--a progressive, irreversible brain disorder--is a formidable opponent with no known cause or cure. More than 4.5 million Americans are thought to have this disease that attacks and slowly steals the minds of its victims. Alzheimer's impacts every nation where life expectancy has increased; estimates indicate that there are now 18 million people worldwide with the disease.

One of the hallmarks of the always-fatal disease is the accumulation of protein amyloid plaques between nerve cells in the brain. Beta-amyloid is a protein fragment that normally is broken down and eliminated in a healthy brain. With Alzheimer's, these fragments form hard, insoluble plaques. Prior to the development of PIB and use of PET imaging, the presence of plaque could be confirmed only during autopsy. "Buildup of beta-amyloid in the brain is thought to be the underlying cause of Alzheimer's disease. Extensive deposits of beta-amyloid are found throughout the brains of all patients with Alzheimer's disease," said Rowe.

Researchers at Austin Health's Centre for PET studied more than 150 subjects with PIB PET and a detailed battery of psychometric tests of memory and other brain functions. PET is a highly specialized, noninvasive imaging technique that uses short-lived radioactive substances to produce three-dimensional images of those substances functioning within the body. "We found that apparently normal elderly subjects with positive PIB PET scans do have mild--but significant--reduction in memory test scores, and this is related to the amount of amyloid present," explained Rowe.

He said that "excess" beta-amyloid is likely related to the fundamental cause of Alzheimer's disease, probably preceding cognitive decline by up to 10 years. Besides providing an accurate diagnosis of early Alzheimer's disease, this research is helpful in providing the possibility of early diagnosis and intervention for individuals who are minimally impaired, subject selection for anti-beta-amyloid clinical trials and monitoring of the effectiveness of anti-beta-amyloid treatments, said Rowe.

"Additionally, 20 percent of the normal volunteers in our study whose average age was 72 had a positive scan. In subjects with mild cognitive impairment (MCI)--a condition that leads to Alzheimer's dementia in about 60 percent of cases--we found positive scans in 60 percent of the subjects. The amount of amyloid present, measured by the PIB scan, related to the severity of memory impairment in these subjects," said Rowe. "Importantly, we and other researchers using PIB PET have also observed that by the time dementia has developed--and a diagnosis of Alzheimer's disease can be made by a clinician--the decline in cognitive function then continues without a further increase in amyloid, highlighting the need for early intervention and prevention of dementia," he added.

"Long-term follow-up of our subjects is underway to more conclusively show that our asymptomatic individuals and MCI subjects with positive PIB scans have the early 'preclinical' stages of Alzheimer's disease," noted Rowe.

Scientific Paper 193: C.C. Rowe, S. Ng, W. Browne, U. Ackermann, S. Gong, G. Chan, G. O'Keefe, H. Tochon-Danguy, V.L. Villemagne, Centre for PET, Austin Hospital, Melbourne, Victoria, Australia; K. Pike, G. Savage, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Melbourne, Victoria, Australia; C.L. Masters, Pathology, University of Melbourne, Melbourne, Victoria, Australia, "Aâ Burden Correlates With Memory Impairment in Non-demented Subjects but Plateaus in Established Alzheimer's Disease: A PIB-PET Cross-Sectional Study," SNM's 54th Annual Meeting, June 2--6, 2007.