Originally Published: August 16, 2008 9:06 p.m.
Scientists have long questioned whether the abundant amounts of amyloid plaques found in the brains of patients with Alzheimer's actually caused the neurological disease, or were just a by-product of its progress.
Now, using new research techniques, scientists have shown that a two-molecule aggregate (or dimer) of beta-amyloid protein fragments may play a role in initiating the disease.
The study, supported by the National Institutes of Health and its National Institute on Aging (NIA), suggests a possible new target for developing drug therapies to combat the irreversible and progressive disorder. Details appeared in the June 22 issue of Nature Medicine.
Alzheimer's disease is marked by the build-up of plaques consisting of beta-amyloid protein fragments, as well as abnormal tangles of tau protein found inside brain cells. Early in the disease, Alzheimer's pathology is first observed in the hippocampus, the part of the brain important to memory, and gradually spreads to the cerebral cortex, the outer layer of the brain.
In this study, researchers tested cerebral cortex extracts from brains donated for autopsy by people aged 65 and older with Alzheimer's, as well as those without dementia. The extracts contained soluble one-molecule (monomer), two-molecule (dimer), three-molecule (trimer) or larger aggregates of beta-amyloid, as well as insoluble plaque cores. The researchers then injected the extracts into normal rats or added the extracts to slices of normal mouse hippocampus.
Researchers discovered that both the soluble monomers and the insoluble plaque cores had no detectable effect on the hyppocampal slices. However, the soluble dimers induced certain key characteristics of Alzheimer's in the rats. The dimers impaired memory function, specifically the memories of newly learned behaviors. The dimers also reduced by 47 percent the density of the dendrite spines that receive messages sent by other brain cells.
"Scientists have theorized for many years that soluble beta-amyloid may be critical to the development and progression of this devastating disease. Now these researchers have isolated a candidate causative agent from brains of people with typical Alzheimer's," said NIA Director Richard J. Hodes, M.D. "While more research is needed to replicate and extend these findings, this study has put yet one more piece into place in the puzzle that is Alzheimer's."
For more information on aging-related research and the NIA, please visit www.nia.nih.gov. The NIA provides information on age-related cognitive change and neurodegenerative disease at its Alzheimer's Disease Education and Referral Center site at www.nia.nih.gov/Alzheimers.