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A new century of Alzheimer's disease research

Alzheimer’s research world: to what degree is AB responsible for the neurodegeneration seen in the disease"

No one knows what AB “normally” does inside the brain. “That is the biggest secret in Alzheimer’s disease research,” says Dr. Caselli. “We’d like to know what role it plays.”

And no one understands how tau interacts with AB.

Mayo Clinic researchers know a lot about tau, which helps stabilize the roadlike microtubules that run inside nerve cell bodies. In the world of neurobiology, tau is the big player, responsible for about 30 forms of neurodegeneration, including frontotemporal dementia, the second most common form of dementia after Alzheimer’s.

Alzheimer’s disease is the only form of dementia in which AB is involved.

As Alzheimer’s develops, the shape of tau molecules inside neurons changes; they begin to come off the microtubules they had once supported, and bind together into paired and twisted filaments. “The hypothesis is that AB stresses neurons, releasing cascades of signals that affect the phosphorylated state of tau bound to microtubules, causing them to be released,” says Dr. Hutton. This process proves to be toxic to the microtubules, which in turn cannot transport the molecular cargo needed to keep the neuron alive.

“Either the roads provided by the microtubules break down because of loss of tau, or tau accumulates into tangles that block these roads,” he says. “We don’t have evidence as to whether it is the tangles or the loss of tau that is causing cell death.

“The tangles we see are an end-stage event, whereas there is plenty of tau aggregation that occurs before these roadblocks appear,” says Dr. Hutton. “In any case, the brain can’t cope without tau.”

Because of the connection between AB and tau loss, the Mayo Clinic researchers believe that if AB is treated before the onset of tau damage, progression of the disease can be prevented. “We also know that tau is responsible f
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