Brain Changes in Young Adults at Risk for Alzheimer's Disease
Banner Good Samaritan Scientists discovery could help predict genetic disease.
PHOENIX (December 16, 2003) – Researchers have detected the earliest known brain changes in people at risk for Alzheimer's disease. Brain abnormalities were detected in healthy young adults carrying a common susceptibility gene for Alzheimer's, more than four decades before the possible onset of memory and thinking problems. Eric Reiman, M.D., Scientific Director of the PET Center at Banner Good Samaritan Medical Center in Phoenix, Arizona, and his colleagues reported these findings today in the Proceedings of the National Academy of Sciences.
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Alzheimer's disease is the most common form of memory and thinking problems in older people, affecting about 10 percent of people over60 and almost half of those over 85. The "apoE4 gene," which is found in almost one-fourth of the population, increases a person's susceptibility to the development of Alzheimer's disease at these older ages.
In the new study, the researchers used a brain-imaging technique called positron emission tomography (PET) to measure glucose metabolism, an indicator of brain activity, in healthy adults in their 20s and 30s. Powerful computer programs were used to map the differences in brain activity between 12 people who carried a copy of the apoE4 carriers and 15 people who did not carry this gene. Although the individuals carrying the apoE4 gene performed normally on the memory and thinking tests, Reiman and colleagues found that they had abnormally low brain activity in the same regions of the brain as patients with the clinical diagnosis of Alzheimer's disease.
"These findings underscore the possibility of finding treatments to prevent Alzheimer's disease at the earliest possible time and in the most effective way," said Reiman, who is also Professor of Psychiatry at the University of Arizona, Clinical Director of the Translational Genomics Research Institute, and Director of the Arizona Alzheimer's Disease Consortium. "Also, they reinforce the possibility of using PET to help establish the effectiveness of these prevention therapies without having to wait many years to determine whether or when the research volunteers develop symptoms."
Meantime, Dr. Reiman cautions that PET should not be used as a clinical screening device to assess the risk of Alzheimer's disease in healthy persons, since it cannot predict with sufficient certainty whether or when a person might develop symptoms of this catastrophic disorder.
Based on previous research, it is believed that the reductions in brain activity found in patients experiencing Alzheimer's disease symptoms, and in older people who are cognitively normal but at genetic risk for the disorder, become more severe as these individuals grow older. Studies led by Reiman and previously published in the New England Journal of Medicine and the Proceedings of the National Academy of Sciences found that 50- to 65-year-old carriers of the apoE4 gene had abnormally low brain activity in the same brain regions as clinically affected patients, that this activity continues to decline over time, and that PET could efficiently test the potential of treatments to prevent Alzheimer's disease.
"These findings raise several interesting and important questions," says Richard Caselli, MD, Professor and Chairman of Neurology at the Mayo Clinic, Scottsdale, and another member of the Arizona research team. "Can these brain changes also be found in healthy persons who have other genetic and non-genetic risk factors for Alzheimer's disease? How early before or after birth are the initial brain changes seen in those susceptible to Alzheimer's disease? To what extent do the underlying brain changes provide a foothold for the development of the microscopic and metabolic abnormalities found later in life in patients with Alzheimer's disease? And can those brain changes be targeted by an extremely safe and well tolerated prevention therapy?"
Working with their colleagues at the Translational Genomics Research Institute in Phoenix, the Arizona researchers are particularly interested in characterizing the underlying brain changes responsible for these remarkably early metabolic changes, which appear to precede the microscopic brain abnormalities (known as plaques and tangles) found in patients with Alzheimer's disease. By investigating genes that are selectively turned on or off in the metabolically affected regions of donated brains, the scientists hope to provide molecular targets against which one could aim putative drugs for the primary prevention of this disorder.
Other participating scientists include Kewei Chen, PhD; Gene E. Alexander, PhD; Daniel Bandy, MS, CNMT; David Osborne, PhD; Ann Saunders, PhD; and John Hardy, PhD. The participating research institutions include Banner Good Samaritan Medical Center; Mayo Clinic Scottsdale; the University of Arizona; Arizona State University; Duke University; Mayo Clinic, Jacksonville; the Translational Genomics Research Institute; and the Arizona Alzheimer's Disease Consortium.
The Arizona Alzheimer's Disease Consortium, which includes the state-supported Arizona Alzheimer's Research Center and the National Institute on Aging-sponsored Arizona Alzheimer's Disease Core Center, is a statewide research laboratory without walls dedicated to the scientific understanding, early detection, treatment, and prevention of Alzheimer's disease.
This study was supported by grants from the Alzheimer's Association, the National Institute on Aging, the National Institute of Mental Health, and the state of Arizona.
