A novel receptor in the brain, which is extremely sensitive to beta-amyloid peptide (AB) and may play a key role in early stages of Alzheimer's disease has been identified by scientists.
Led by Dr. Jie Wu at Barrow Neurological Institute, the study has identified a new candidate for therapeutic intervention in Alzheimer's.
The novel receptor was found in the basal forebrain, an area of the brain that plays a critical role in memory and learning and is one of the first areas of the brain to degenerate with Alzheimer's.
The degeneration is linked with losses of the chemical messenger, acetylcholine, and some of the molecules that translate acetylcholine's messages, called nicotinic receptors. The formation of large aggregates or plaques of AB is also a characteristic of Alzheimer's disease.
However, the researchers have no clue how these two features are interrelated.
The researchers made the unexpected finding during a study examining effects of AB on basal forebrain nicotinic receptors.
They first found that acetylcholine signalling at those receptors was highly sensitive to blockage even by low levels of AB.
They also found that AB as small aggregates-and not large plaques of AB-had this same blocking effect.
And then it was found that the type of nicotinic receptors showing this high sensitivity to AB has a different composition than other nicotinic receptor types previously identified and shown to be less sensitive to AB.
"We now believe that most of the nicotinic receptors in the basal forebrain have this unique composition and high sensitivity to AB. Our hypothesis is that as AB begins to increase, it first blocks acetylcholine signaling at these receptors, perhaps triggering events that eventually lead to neurodegeneration," said Wu.
The study has been published in the Journal of Neuroscience.