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Two cardiovascular proteins pose a double whammy in Alzheimer's
Date:12/21/2008

flow decreased.

The latest report goes further, implicating the molecular duo in the slowed removal of amyloid beta. The team found that SRF and myocardin working together turn on a molecule known as SREBP2. That protein inhibits a molecule known as LRP-1, which helps the body remove amyloid beta. In other words, when SRF and myocardin are active, toxic amyloid beta accumulates.

The findings came primarily from the team's studies of brain cells taken from people who had Alzheimer's disease and comparing them to cells from healthy elderly people.

Compared to the smooth muscle cells from healthy adults, the cells from patients with Alzheimer's disease had about five times as much myocardin and four times as much SRF, about five times as much SREBP2, and about 60 percent less LRP-1. That translated into a reduced ability to remove amyloid beta: Cells taken from patients with the disease had only about 30 percent of the ability to remove the substance as cells taken from their healthy counterparts.

When the team lowered levels of SRF to the same level that exists in healthy cells, the cells from Alzheimer's patients improved in their ability to remove amyloid beta, doing it just as well as cells from healthy individuals. Conversely, when the team boosted levels of SRF and myocardin in the healthy cells, the changes lowered by about 65 percent those cells' ability to remove amyloid beta.

In mice, the team found parallel results. When the team boosted SRF or myocardin in healthy mice, those mice had about twice as much SREBP2 in their smooth muscle cells in the brain's blood vessels. They also had 90 percent less LRP-1, three times as much amyloid beta in their arteries, and 70 percent more amyloid beta in their brain tissue.

When the team reduced SRF and myocardin in mice prone to developing Alzheimer's disease, those mice had 60 percent less SREBP2, about four times as much LRP-1, and a 50-percent reduction in amylo
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
Source:Eurekalert

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