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What Underlies Alzheimer’s

Biologists Michelle King and George S. Bloom have made an essential advance in the fight against Alzheimer’s disease. Research by these UVA professors has identified a heretofore unknown interaction between neural proteins called beta-amyloid and tau that leads to their transformation into plaques and tangles, respectively. These plaques and tangles are what lead to brain cell death in Alzheimer’s; the plaques attack neuron cells from the outside, and the tangles attack from within. It was previously thought that these were two independent processes, and that only the tangles were essential to Alzheimer’s.

In a study in the Journal of Cell Biology, King and Bloom added pre-plaque beta-amyloid to neurons with and without the tau protein; non-tau cells showed no adverse effects, but cells in which the pre-plaque beta-amyloid and tau interacted had widespread degeneration of microtubules along the neuron’s axon. When the microtubules break down, the synapses along the axon shut down and the neuron cell dies. This is what causes the irreversible loss of memory and cognitive abilities in Alzheimer’s patients. Because tau is only found in nerve cells, this crucial interaction also helps explain why Alzheimer’s specifically targets nerve cells.

“We think we’ve found one of the seminal cell biological events in the development of Alzheimer’s disease,” Bloom says. “If we can figure out all of the steps in the process and understand each player at every step, every new player will represent a potential new drug target for Alzheimer’s therapy.”