Receptors Support Amyloid Theory Of Alzheimer's

The deposition of amyloid into senile plaques is one of the hallmarks of Alzheimer's disease, and some scientists believe that beta amyloid is the factor that initiates and promotes the neurodegeneration which characterizes the disease. Evidence for this rests on the close association of beta amyloid with degenerating neurons in the brains of sufferers, and the fact that some inherited forms of the disease are linked to mutations in beta amyloid precursor protein.

Beta amyloid, which is normally produced in soluble form in the brain, has been shown to disrupt the ion balance of neurons and also stimulates microglial-mediated inflammatory reactions which may contribute to the neurodegenerative process. In addition, beta amyloid seems to induce oxidative stress via the production of free radicals. How beta amyloid achieves this has become one of the missing pieces in the puzzle of Alzheimer's pathology, but now two papers in Nature (August 22) have suggested mechanisms by which it may come about.

RAGE Involved In the first Nature paper, Yan et al report that beta amyloid interacts with a cell-surface receptor called RAGE (receptor for advanced glycation end-products) on neurons, microglia and vascular endothelial cells. Not only is oxidative stress induced when beta amyloid binds to RAGE, but the receptor is abundant on microglia and induces their activation. Furthermore, increased expression of RAGE in Alzheimer's disease brain tissue indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.