For some time, scientists have blamed Alzheimer's disease on a small molecule called amyloid beta protein (A beta) that leaves large gummy deposits in the brain. Recent studies suggest that these A beta proteins stick together to form floating toxic clumps that kill brain cells. Now, UCLA scientists have identified a tiny loop in A beta as the likely culprit behind the adhesion process.

©University of California
Amyloid Protein Loop. Broken red lines indicate a loop in the amyloid B-protein that enables it to attach to other proteins and form clumps that kill brain cells.


The UCLA team discovered that gene mutations in A beta increase the loop's flexibility, enabling it to join easily with loops from other A beta proteins and form clumps. The loop also appears in the region of the protein that regulates how - and how much - A beta is made.

Current drugs treat the symptoms of Alzheimer's but not the disease's underlying cause. By shedding light on how toxic A beta formations arise in the brain, the UCLA discovery could aid the design of new drugs that both block the production of A beta and prevent it from clumping.

Alzheimer's disease afflicts some 5 million Americans and an estimated 24 million people worldwide. Half of people over 85 may suffer from the fatal disorder, which slowly robs individuals of their memory and ability to think and function independently.

The principal investigator is David Teplow, professor of neurology at the David Geffen School of Medicine at UCLA. The Proceedings of the National Academy of Sciences published the findings in its Oct. 10 online early edition.

The National Institute of Neurological Disorders and Stroke, the National Institute on Aging and the Alzheimer's Association supported the study.

Adapted from materials provided by University of California