Amyloid Plaques and Neurofibrillary Tangles

Illustration showing the differences between a normal brain and an Alzheimer's diseased brain

What are Amyloid Plaques?

Amyloid is a general term for protein fragments that the body produces normally. Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. Amyloid plaques are hard, insoluble accumulations of beta amyloid proteins that clump together between the nerve cells (neurons) in the brains of Alzheimer’s disease patients.

What Causes Beta Amyloid Plaques?

Beta amyloid molecules are initially found in very small strands that can dissolve in the fluid between cells, which will be washed out of the brain. However, the enzyme that cuts APP into beta amyloid is not very precise and can also result in slightly larger strands that do not dissolve. The longer strands are very ‘sticky’ at the level of individual molecules and start the process of clumping into the deposits referred to as plaques.

Can Amyloid Plaques Be Dissolved or Reduced?

This question has been the focus of drug development for many years. BrightFocus has funded the work of scientists who have shown various methods of clearing away plaques. For example, Dr. Matthew Campbell (Trinity College) has experimented with temporarily disrupting the blood-brain barrier to clear out existing plaques. After many heartbreaking clinical trial failures, there is growing concern among the scientific and medical communities that clearing plaques may not be sufficient to treat the disease. This is a very active area of research.

What are Neurofibrillary Tangles?

Neurofibrillary tangles are insoluble twisted fibers found inside the brain's cells. These tangles consist primarily of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. In Alzheimer's disease, however, the tau protein is abnormal and the microtubule structures collapse.

What Causes Neurofibrillary Tangles to Form?

Tangles form when tau is misfolded in a very specific way. In Alzheimer’s disease, the tau forms a C-shape in the core of the tangle with a loose end sticking out randomly. In Pick’s disease, the core forms a J-shape instead. Once a tangle has been started, more tau proteins are recruited to make it longer. There is likely a molecule responsible for shaping tau into these forms, but (as of the time of writing) it has not yet been identified.

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How Do Plaques and Tangles Cause Dementia?

The presence of plaques around a neuron causes them to die, possibly by triggering an immune response in the immediate area. Tangles form inside of neurons and interfere with the cellular machinery used to create and recycle proteins, which ultimately kills the cell.  

How Can Plaques and Tangles Be Prevented?

This is not known. Proper diet and regular exercise are known to limit the formation of plaques and tangles. For more, visit other resources available on this site or the National Institutes of Health.

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This content was first posted on: July 1, 2015
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