Alzheimer’s disease is the most common form of dementia, with symptoms affecting memory, thinking and behavior that grow progressively worse over time, eventually causing death. The cause of Alzheimer’s is not well understood, but it is associated with two physiological hallmarks – plaques that build up between neurons in the brain and tangles of protein that pile up inside those cells.
Several labs at Rockefeller work to elucidate the processes underlying Alzheimer’s.
Paul Greengard, who won the 2000 Nobel Prize in Physiology or Medicine for research into how neurons communicate, recently discovered how blockbuster cancer drug Gleevec binds to a protein that stimulates the production of amyloid-β, the protein that makes up the Alzheimer’s plaques. The development of a molecule with similar activity that can cross the blood-brain barrier, unlike Gleevec, represents a potential new anti-amyloid therapy for Alzheimer’s.
Greengard and Nathaniel Heinz developed a technique, called TRAP, that can identify all of the proteins produced by a given cell-type, which is being applied to understand how Alzheimer’s and other diseases operate at a finer level of detail than previously possible.
And Jeffrey Ravetch has identified a marker in the blood that could help doctors determine an individual’s predisposition to Alzheimer’s, which could enable early intervention once effective therapies are discovered.
Recent research at Rockefeller has also focused on the less studied vascular component of the disease.
Sidney Strickland has found that a clotting agent in the blood, called fibrinogen, interacts with the plaques, creating blood clots that are harder than usual to break down and that could starve neurons of their regular oxygen supply. His lab is identifying small molecules that could interfere with the plaque-fibrinogen interaction that could provide an effective drug therapy for the disease.