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Yerkes Researchers Closer to Determining Why Humans Develop Alzheimer's Disease

March 30, 2009

Finding Could Shed Light on Why Only Humans Develop Neurodegenerative Diseases and Pave the Way for New Treatment Approaches

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Lisa Newbern, 404-727-7709,

ATLANTA – Researchers at the Yerkes National Primate Center, Emory University, have discovered a compound used to diagnose Alzheimer’s Disease in humans may also be useful in determining why humans develop the disease and other primates do not. The study, available in the current online issue of Neurobiology of Aging, has moved the scientific community another step closer to understanding why age-related neurodegenerative diseases, such as Alzheimer’s Disease, are uniquely human and is providing new insights into potential therapeutic targets for these disorders.

The study focused on Pittsburgh Compound B (PIB), a radiolabeled compound used to diagnose Alzheimer’s Disease in humans by positron emission tomography (PET). When injected into the bloodstream, PIB enters the brain and binds to the beta-amyloid plaques that are thought to be a key feature of Alzheimer’s Disease.

The brains of nonhuman primates generate beta-amyloid protein that has the same amino acid sequence as that in humans. Furthermore, monkeys and great apes develop abundant beta-amyloid plaques as they age. Nonhuman primates, however, do not become demented, nor do they have some of the other brain lesions typical of Alzheimer’s Disease. To determine if there is a structural difference in the beta-amyloid proteins humans and nonhuman primates produce, the researchers used PIB to analyze post-mortem brain tissue from aged rhesus macaques, squirrel monkeys, chimpanzees, humans with end-stage Alzheimer’s Disease and humans with aged but healthy brains.

Lead researchers Rebecca Rosen, a doctoral student who is conducting her research at Yerkes, and Lary Walker, PhD, a neuroscientist and research professor at Yerkes, in collaboration with Harry LeVine III, PhD, at the University of Kentucky, found PIB does not bind to beta-amyloid protein in the brains of the nonhuman primates, even if the brain contained more beta-amyloid protein than a human counterpart. This finding indicates “PIB may be useful in determining why humans develop Alzheimer’s Disease and other primates do not,” explained Dr. Walker.

As many as five million Americans are living with Alzheimer’s Disease, the most common form of dementia. “A cure has eluded researchers, and the disease is progressive and fatal,” stated Rosen. “That’s why it’s so important we narrow in on the huge number of potential causes of Alzheimer’s Disease,” she continued. “By studying the development of human features of the disease that occur naturally in nonhuman primates, we may be able to isolate what makes people so susceptible to neurodegenerative disease and identify targets for therapeutics.”

To follow up the study, Walker and Rosen are trying to determine if high-affinity PIB binding sites can be created in transgenic Alzheimer’s mouse models by exposing them to Alzheimer’s brain extracts that strongly bind to PIB. This could yield a mouse model that more closely resembles Alzheimer's Disease as it occurs in humans “If PIB binding differs between humans and nonhuman primates, we also want to know if PIB binding differs among human cases and whether this is related in any way to the pathology in the brain,” said Walker.

For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of Health–funded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.

Within the fields of microbiology and immunology, neuroscience, psychobiology and sensory-motor systems, the center’s research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer’s Disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Parkinson’s and Alzheimer’s; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

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