Creation of a Fibroblast/iPS Cell Bank to Facilitate Peripheral/Brain Comparisons, and Allow Molecular Investigations into Molecular Mechanisms Underlying Differences in Disease Aggressiveness

An astonishing discovery of how to convert skin cells into other kinds of cells—including brain cells—earned Dr. Shinya Yamanaka the Nobel prize in 2012 and already has opened extraordinary new capabilities in science. Applied to Alzheimer’s disease, it has the potential to revolutionize how we do experiments. Right now, we rely on examining brain tissue of patients who have died of the disease to understand the molecular changes that occur, but the promise of Dr. Yamanaka’s discovery is that we could use a little piece of skin—from a living patient—instead. The major barrier to doing this is that we do not know whether the “brain” cells that can be made in a few weeks from a piece of skin actually act like the cells from a brain of a person who has been alive for 70 or 80 years. We propose to create a bank of skin cells taken from the same people who now donate brain tissue at autopsy to directly compare the two, and to make this resource available to the dozens (hundreds) of labs that have developed specialized assays in which comparison of the two different kinds of “brain” cells would be valuable. Our own studies will be directed to understanding whether there are different molecular characteristics in “brain” cells made from the skin of patients whose course of disease was more aggressive—or more benign—to try to develop methods to understand this dichotomy.