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2 defective proteins conspire to impair the nerve cell's 'powerhouse' in Alzheimer's disease
Date:5/13/2011

es in neurons. In recent years scientists like Johnson have been focusing on an abnormally shortened form of the protein, known as truncated tau, as one that likely has a role in Alzheimer disease.

Johnson's team looked at the performance of mitochondria in rat neurons during exposure to amyloid beta, to the regular tau protein, to the truncated version of tau, and to combinations of amyloid beta and the two versions of tau. Among the experiments was one in which scientists tracked the movement of mitochondria, snapping a new image every 10 seconds during a five-minute span to track the movements of the organelles within neurons.

The biggest changes to mitochondria occurred when amyloid beta and truncated tau were present together. Effects included:

  • The ability of mitochondria to maintain their electrical potential, which is needed to produce energy efficiently, was severely impaired. They had only one-third of the electrical potential of mitochondria in control cells.

  • Mitochondria usually are highly mobile and distributed throughout the cell. However, in the presence of truncated tau and amyloid beta, mitochondria clumped together abnormally in some parts of neurons and failed to get to other parts of neurons, such as the synapses, like they normally do. Overall, only about half the mitochondria were mobile compared to their counterparts not exposed to the pathological proteins.

  • Cells that were exposed to both truncated tau and amyloid beta were less able than usual to respond to cellular stress. The number of harmful molecules known as reactive oxygen species or free radicals was boosted 60 percent in these cells.

  • Mitochondria exposed to amyloid beta and truncated tau were fragmented, with the average length just half that of normal mitochondria.

The cellular changes that Johnson is looking at likely occur before a patient begins to experience symptoms like memory loss. Most scientists bel
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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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