The study, which was supported by the "Oligomer Research Consortium" of the Cure Alzheimer Fund and a MERIT Award from the Veterans Administration, appears in the journal Annals of Neurology.
"The buildup of amyloid plaques was described over 100 years ago and has received the bulk of the attention in Alzheimer's pathology," said lead author Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer's Disease Research Center, Mount Sinai School of Medicine. "But there has been a longstanding debate over whether plaques are toxic, protective, or inert."
Several research groups had previously proposed that rather than plaques, floating clumps of amyloid (called oligomers) are the key components that impede brain cell function in Alzheimer's patients. To study this, the Mount Sinai team developed a mouse that forms only these oligomers, and never any plaques, throughout their lives.
The researchers found that the mice that never develop plaques were just as impaired by the disease as mice with both plaques and oligomers. Moreover, when a gene that converted oligomers into plaques was added to the mice, the mice were no more impaired than they had been before.
"These findings may enable the development of neuroimaging agents and drugs that visualize or detoxify oligomers," said Dr. Gandy. "New neuroimaging agents that could monitor changes in Abeta oligomer presence would be a major advance. Innovative neuroimaging agents that will allow visualization of brain oligomer accumulation, in tandem with careful clinical observations, could lead to breakthroughs in managing, slowing, stopping or even preventing Alzheimer's.
"This is especially important in light of research reported in March showing that 70 weeks of infusion of the Abeta immunotherapeutic Bapineuzumab® cleared away 25 percent of the Abeta plaque, yet no clinical benefit was evident."
The Mount Sinai team included Michelle Ehrlich, MD, Professor of Pediatrics, Neurology, and Genetics and Genomic Sciences, and John Steele, a Mount Sinai graduate student, who performed the key analyses of the behavioral data. Dr. Charles Glabe, an oligomer expert and a member of the Cure Alzheimer Fund research consortium, is also a co-author of the paper. Dr Gandy is also a neurologist at the James J Peters Veterans Affairs Medical Center, an affiliate of Mount Sinai School of Medicine.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2009, U.S. News & World Report ranked The Mount Sinai Hospital among the nation's top 20 hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
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