Over the last decade, clinical drug trials have all targeted Amyloid – yet there was always a question as to whether or not Amyloid was truly the key player. Here is the story.

How Amyloid Became the Prime Suspect

The story of Alzheimer’s is like a murder mystery.  Nerve cells are dying and all that is left at the scene are fingerprints:  Amyloid plaques (abnormal groupings of protein fibers) and Tau tangles (tangled protein connections in the transportation system of the nerve cells).

Looking at the evidence or breakdown in the brain, scientists have asked key questions and created several scenarios. Why did this breakdown occur? What caused it? What was happening in the brains of those who developed Alzheimer’s for this to happen?  Based on what they saw, scientists suspected that either Amyloid in the plaque or Tau in the tangle causes Alzheimer’s disease. 
But, which one?  Tau, it turns out, is the only abnormality found in over 20 dementias, especially frontotemporal dementia.  However, in many models of Alzheimer’s disease, Amyloid deposits precede Tau tangles. 

We know that memory loss is the primary symptom of Alzheimer’s. In normal brains, Amyloid is found in the part of the cell, the dendrite, known to be the physical basis of memory. However, in imaging studies of people at risk for late onset Alzheimer’s, we see that Amyloid levels rise as memory declines. Thus scientists presumed that Amyloid was the mastermind and Tau simply the accomplice. 

Scientists then targeted amyloid in their clinical trials using several different agents to prevent or destroy the Amyloid deposits.  In July, 2008 at the International Conference of Alzheimer’s Disease (ICAD), the results of these Amyloid targeted treatment trials were revealed.  Unfortunately, none of these Amyloid bullets worked.

Back to the Crime Lab:  Tau is the New Suspect

Researchers are returning their attention to Tau for the causes of Alzheimer’s.  Looking through the microscope, studies show that Tau pathology in Alzheimer’s disease is better correlated to cognitive deficits than Amyloid deposits.  Special brain imaging techniques show breakdowns in cellular transportation even before the Amyloid plaque deposits form. 

Several new treatments are currently in trial:  Methylthionium, an old antibiotic from the 1930s, which inhibits collected masses of altered Tau proteins; and Dimebon, an older antihistamine that boosts mitochondria, the energy producing component of nerve cells needed to help prevent Amyloid deposits.

In the meantime, stay tuned for the results of these trials as the crime search continues. We hope to learn more at the International Conference on Alzheimer’s Disease when it convenes in July, 2009.