New Advances for Alzheimer’s Disease
Researchers from Yale University Department of Physiology in the College of Medicine (Ji Won Um, Adam C. Kaufman, Mikhail Kostylev et al) have gained new insights into the potential etiology of Alzheimer’s disease based upon their observations of the toxicity of amyloid-beta oligomer-coupling with the mGluR5 receptor. Amyloid plaques are accepted as the anatomical hallmark of Alzheimer’s disease, and the misprocessing of amyloid precursor protein is clearly a biological trigger of that disease. But many open questions remain with respect to which parts of the misprocessed protein are so toxic, and why. The new findings follow up on earlier studies showing that amyloid-beta oligomers bind to normal prion proteins.
A prion is a nonliving, infectious agent made of misfolded protein. It can reproduce by making normal, healthy proteins misfold themselves with the aid of its host’s biological machinery, like a virus. “Prion” is short for “proteinaceous infectious particle.”
In the new set of experiments, the scientists showed that the complex of bound oligomer and prion protein activates a glutamate receptor, and that this activation led to increased calcium influx into neurons, to their detriment.
Blocking the glutamate receptors in mice transgenic for familial Alzheimer’s disease genes reversed synaptic damage, as well as learning and memory deficits. The findings appeared in the Sept. 4, 2013, issue of Neuron.
Here at WCCTG we have participated in many early and late stage development new drug development programs for Alzheimer’s disease. We have perfected the procedure to determine if a new drug can actually gain access to the central nervous system by collecting samples of cerebral spinal fluid (CSF) by single “spinal taps” or by acquiring multiple CSF samples throughout a 24–36 hour sampling time.