Untangling Alzheimer's
Every 66 seconds, someone in the United States develops Alzheimer’s disease, a progressive neurological condition that inexorably destroys the brain’s cognitive circuits, kills more people annually than breast and prostate cancers combined, and exacts enormous personal and societal tolls.?
The major risk factor for the common, late-onset form of Alzheimer’s is age itself. A team of researchers from Yale School of Medicine has examined what molecular and cellular-level changes with advancing age make the neurons affected by Alzheimer’s so vulnerable to tau pathology, where the neurons fill with neurofibrillary tangles and die.?Tau is a protein that helps to stabilize the cell’s cytoskeleton.??
A key factor, the researchers say, is loss of calcium regulation.
Amy Arnsten, the Albert E. Kent professor of neuroscience and psychology and a senior author on the paper, explains that?the neuronal circuits responsible for higher cognitive functions — memory, learning, thinking — have specialized molecular properties. “Neurons?involved with these functions have to activate themselves without sensory stimulation, a process that requires high levels of calcium. But the calcium must remain tightly controlled. If the regulation of calcium is lost, calcium can initiate toxic actions within the neurons.”
领英推荐
The researchers, from the labs of both Arnsten and Angus Nairn, found that?the proteins that normally regulate calcium signaling in younger brains diminish with age, resulting in the calcium’s “leaking” out of “safe storage” in the smooth endoplasmic reticulum and into other parts of the cell. Their findings were published in?Alzheimer’s and Dementia, the Journal of the Alzheimer’s Association.
This disruption of calcium storage correlates with a process in which the tau becomes phosphorylated — meaning that phosphates attach themselves to the proteins and disrupt their functioning. “When the tau is phosphorylated,” Arnsten says, “it changes shape, ultimately leading to the neurofibrillary tangles that are a hallmark of Alzheimer’s, and to profound cognitive impairment.” Finding ways to restore calcium regulation could slow the disease progress, or offer promising pathways to treatment.?
Originally published in the July/August 2021 issue of Yale Alumni Magazine
thanks! there is also a lovely small book 7 1/2 lessons on the Brain written by a female neuroscientist that gently and with humor erases /replaces all we were certain about in the last 50 years - a better understanding of the brain will help degenerative diseases as well.
Higher Education Professional
3 年Hi Rhea! This is interesting and hopeful news on Alzheimer’s. It wasn't that long ago when scientists were looking for the connection between tau and the disease.