Washington, August 15 (ANI): Researchers at the Salk Institute for Biological Studies have found that when alpha-7, a key nicotine receptor that plays a role in cognitive processes, encounters beta amyloid, the toxic protein found in the hallmark plaques of Alzheimer's disease, the two may actually go rogue.
In combination, say the researchers, alpha-7 and beta amyloid appear to exacerbate Alzheimer's symptoms, while eliminating alpha-7 seems to nullify beta amyloid's harmful effects.
The researchers sought to determine whether the alpha-7 receptors actually modulate the effects of beta amyloid in Alzheimer's disease.
"Alpha-7 is expressed all over the brain. All mammals have it, and it's probably essential for something, but we don't know what," says Dr. Stephen F. Heinemann, of the Salk Molecular Neurobiology Laboratory, where the study was carried out.
For their study, the researchers crossed mice engineered to lack the gene for alpha-7 with a mouse model for Alzheimer's disease, which had been genetically engineered to overexpress amyloid precursor protein (APP), an antecedent to beta amyloid.
Putting the offspring through a series of memory tests, the researchers found that those with both mutations-too much APP and no gene for alpha-7-performed as well as normal mice.
However, the Alzheimer's mice, which had the alpha-7 gene and also overexpressed APP, did poorly on the tests.
Pathology studies revealed the presence of comparable amounts of plaques in the brains of both types of mice, but in those lacking the alpha-7 gene, they appeared to have no effect. Similar disparities were evident in measurements of the synaptic function underlying learning and memory.
"All the results together gave us idea that yes, alpha-7 is in part a mediator of the synaptic and cognitive pathology produced by beta amyloid accumulation," says first author Dr. Gustavo Dziewczapolski, a postdoctoral researcher in Heinemann's lab.
Based on their findings, the researchers came to the conclusion that scientists seeking therapeutic targets for Alzheimer's might be more successful if they blocked the function of the alpha-7 receptor or block beta amyloid's access to alpha-7 instead of trying to activate the receptor.
Dziewczapolski and Heinemann plan to continue their investigations of the alpha -7/beta amyloid connection, with the hope of identifying the mechanism behind the relationship and determining why the synapses die in Alzheimer's.
A research article describing the current study has been published in The Journal of Neuroscience. (ANI)