As mystery deepens over the cause of Alzheimer’s, a UB lab seeks new answers

Molecular motors travel on microtubule tracks in a single axon in the nerve cell of a fruit fly larva. This video shows the motors' normal behavior in transporting cargo such as important proteins to different parts of a cell. Credit: Gunawardena Lab at the University at Buffalo

“A lot of the treatments being developed for Alzheimer’s are targeting beta-amyloid, but maybe we should be targeting processes that happen earlier on, before plaques are formed. ”

BUFFALO, N.Y. — For more than 20 years, much of the leading research on Alzheimer’s disease has been guided by the “amyloid hypothesis.”

This theory focuses on one of the disease’s most salient traits: the formation of unusual plaques — or buildups of protein — in patients’ brains. In Alzheimer’s, these plaques are made from a protein known as beta-amyloid. As a result, many scientists believe that removing beta-amyloid or inhibiting its clumping should help to stave off dementia.

But with a series of failed clinical trials raising questions about this premise, some researchers are looking for deeper explanations into the causes of Alzheimer’s and how this debilitating condition can be treated.

University at Buffalo biologist Shermali Gunawardena is among these investigators.

Her lab studies axonal transport — the complicated, internal highway system that conveys precious, life-giving materials from one part of a nerve cell to another. (Nerve cells, also called neurons, are a category of cells that include brain cells.)

Breakdowns in this transport system can lead to “traffic jams,” and some scientists hypothesize that such blockages precede the formation of plaques in neurological diseases like Alzheimer’s, Gunawardena says.

Using the neurons of fruit fly larvae, her team has been researching the role of presenilin — another Alzheimer’s-linked protein — in axonal transport for several years, with the latest results published on May 22 in the journal Human Molecular Genetics.

“We are looking at processes that occur before cell death, before you start to see plaques in the brain,” says Gunawardena, PhD, an associate professor of biological sciences in the UB College of Arts and Sciences. “A lot of the treatments being developed for Alzheimer’s are targeting beta-amyloid, but maybe we should be targeting processes that happen earlier on, before plaques are formed.