Alzheimer's Club

Among the hallmarks of Alzheimer’s, which include neurofibrillary tangles and amyloid plaques, Abbott Laboratories Inc., Abbott Park, Ill., researchers now say they found a new species of amyloid beta-peptide that selectively binds to nerve cells in the brain and is an important causal factor for the disease.
“For years researchers have focused on finding ways to stop the formation of the plaque, believing that the plaques themselves were toxic,” says James Sullivan, PhD, vice president, neuroscience discovery, Abbott. “Over the last five years, however, more and more research suggests that we did not have the whole story.”

Preclinical research, Sullivan says, now shows that cognitive function, such as memory retention, started being impaired long before amyloid plaques formed. Clinical research also shows that amyloid plaques are present in the brains of aged people without Alzheimer’s.

Thus, the focus has turned to finding other forms of amyloid protein that may represent a toxic or pathologic species. One such form, Sullivan says, is a soluble amyloid, in contrast to the insoluble form found in plaques.

Abbott identified a new soluble globular beta-amyloid species, which they call globulomer, present in the brains of Alzheimer’s patients. “These globulomers are structurally distinct from the [fibrous] form of amyloid that dominates in plaque,” says Sullivan.

Using highly selective antibodies for the globulomers, he says, they were able to prove the presence of this new form of amyloid in the brains of Alzheimer’s patients, which were not present in age-matched controls.

An immunofluorescent imaging technique was used to find the specific sites in the brain where the globulomers bind and found them binding to neurons in the hippocampus, a key region of the brain involved in learning and memory and one of the first areas affected by Alzheimer's disease. Research in mice, Sullivan says, suggests that globulomers inhibit the ability to form and retain memory. They are now conducting research to find the proteins on these neurons, with which the globulomers are interacting.

“The identification of this unique amyloid species provides the opportunity to generate selective antibodies directed against globulomers,” says Sullivan. “Such antibodies have the potential to address the underlying disease pathology, not just the symptoms, and to be safe because of their selective interaction with this toxic species of amyloid.”

Source: Elizabeth Tolchin. Abbott Finds New Amyloid in Alzheimer’s. Drug Discovery and Development. (16 November 2005) [FullText]