Bioethics Blogs

Creative Minds: REST-ling with Alzheimer’s Disease

REST in healthy and Alzheimer's cells

Caption: The REST protein (green) is dormant in young people but switches on in the nucleus of normal aging human neurons (top), apparently providing protection against age-related stresses, including abnormal proteins associated with neurodegenerative diseases. REST is lost in neuron nuclei in critical brain regions in the early stages of Alzheimer’s disease (bottom). Neurons are labeled with red.
Credit: Yankner Lab, Harvard Medical School

Why do some people remain mentally sharp over their entire lifetimes, while others develop devastating neurodegenerative diseases that destroy their minds and rob them of their memories? What factors protect the human brain as it ages? And can what we learn about those factors enable us to find ways of helping the millions of people at risk for Alzheimer’s disease and other forms of senile dementia?

Those are just a few of the tough questions that Bruce Yankner, a 2010 recipient of the NIH Director’s Pioneer Award, has set out to answer by monitoring how gene activity in the brain’s prefrontal cortex (PFC) changes as we age. The PFC is the region of the brain involved in decision-making, abstract thinking, working memory, and many other higher cognitive functions; it is also among the regions hardest hit by Alzheimer’s disease.

A professor of genetics and neurology at Harvard Medical School in Boston, Yankner’s initial work uncovered age-specific changes in activity of certain genes associated with learning and memory [1]. A computational analysis suggested that a master regulator protein, with the awkward name repressor element 1 silencing transcription factor (you can understand why scientists just call this “REST”), may be controlling these genes in older brains.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.