Science and Reason: Alzheimer's disease becomes clearer

One of the interesting things about Alzheimer's disease is that brains of disease victims show, at autopsy, two distinct abnormalities in many of their neurons. But a good explanation of the relationship between these abnormalities has been lacking. Perhaps an explanation is now at hand.

'Missing Link' In Process Leading To Alzheimer's Disease Identified

In Alzheimer’s disease, two kinds of abnormal structures accumulate in the brain: amyloid plaques and neurofibrillary tangles. The plaques contain fibrils that are made from protein fragments called “beta-amyloid peptides.” The tangles also are fibrous, but they are made from a different substance, a protein called “tau.” In the new U.Va. study, the researchers found a deadly connection between beta-amyloid and tau, one that occurs before they form plaques and tangles, respectively.

According to George Bloom, the senior author of the study and a professor of biology and cell biology at U.Va., this connection causes the swiftest, most sensitive and most dramatic toxic effect of beta-amyloid found so far. What makes it most remarkable, though, is that it requires a form of amyloid that represents the building blocks of plaques, so called “pre-fibrillar beta-amyloid,” and it only happens in cells that contain tau. Even though they account for just ~10 percent of the cells in the brain, nerve cells are the major source of tau, which likely explains why they are specifically attacked in Alzheimer’s disease.

Here's the spoiler for the plot of this movie: Tau and pre-fibrillar beta-amyloid together disrupt the network of microtubules within a brain cell. The microtubules make up the transportation network within the cell. Without this network, neurons cannot maintain their synapses with other neurons. Without synapses, the memories that are stored in the connections are lost. And the cell itself is likely to die too.

Synapses are connections between nerve cells, and in the brain they are the structural basis of memory and cognition. When nerve cells in the brain lose their microtubules they also lose the ability to replace worn out synapse parts, and synapses therefore disappear. The loss of synapses, and consequent loss of memories and cognitive skills, cannot be reversed, and can lead directly to nerve cell death.