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The elements of the pathology of Alzheimer’s disease are amyloid plaques, neurofibrillary tangles and inflammation.

In recent years-with the help of research sponsored by Cure Alzheimer’s Fund-a scientific consensus has begun to form about the origin of Alzheimer’s disease. It is believed that the disease develops as a vicious cycle of Abeta peptide accumulation, nerve cell death, and inflammation … which is followed by additional nerve cell death. Genetic and environmental factors can trigger Abeta accumulation, tau tangle formation, and inflammation. Once one part of the pathology is in place, it then acts as a trigger for the other parts; for example, Abeta accumulation can lead to increased inflammation, and vice versa. This cycle then continues, causing more and more damage and nerve cell death. Eventually, this damage becomes so severe that the patient begins to experience a loss in cognitive function.

This model gives a simplified illustration of the emerging consensus and the three basic strategies for intervention:

  • An early-phase intervention, inhibiting the production of the Abeta protein, and/or clearing it from the brain after it forms
  • A mid-phase intervention that would inhibit the formation of Tau tangles and protect neurons from undue stress
  • A late-phase intervention that would fight inflammation and thus slow down or even stop the disease process
“The amyloid plaques build up outside of the nerve cells [in the brain] and now we know that when the nerve cells interact with the plaque, it causes the nerve cell to make a tangle inside,” explains Rudy Tanzi, Ph.D., director of the Alzheimer’s Genome Project and a leading researcher in the field at Massachusetts General Hospital and Harvard Medical School. “And that tangle then chokes the nerve cell from within and kills it. So the killing process begins with the amyloid- that’s kind of the gun-but the tangle is the bullet.”

Experts now believe these amyloid plaques, and the tangles they form, start occurring in people’s brains 10 to 15 years before any symptoms like memory loss begin to show.

 

Using the genetic discoveries of our researchers as guideposts, Cure Alzheimer’s Fund has sponsored dozens of studies investigating the central mechanisms of action behind the Alzheimer’s disease.

 

 

We also have a more thorough understanding of how Alzheimer’s pathology progresses from the earliest to latest stages of the disease. This model of Alzheimer’s allows us to identify three basic strategies for intervention in the process.

The Disease