Tau is a protein abundantly present in the brain. The presence of tau protein is normal and important to maintaining the structure of the nerve cells (aka, neurons) by attaching to the microtubules and by doing so allowing the transmission of signals in the brain and the transport of cargos within the neurons. Phospho-tau, the result of a process known as phosphorylation, is an alteration of tau which can modify and change its structure and function. High levels of phospho-tau deposited in certain areas of the brain are an indicator of Alzheimer's disease.
Tau proteins are necessary to healthy brain function. Think of them as adding support to cells and normal cell function. Tau proteins provide stabilization of microtubules which are crucial to proper cellular shape and functioning . It works like a glue that cements together the filaments that forms the microtubules keeping them straight and stable. Having stable microtubules is very important for the transport of cargos within the nerve cells.
Although it is not abnormal for phospho-tau to exist to some degree in healthy brains, hyperphosphorylation means that there are excessive phosphates attached to tau proteins. This excess of phosphorylated tau can interfere with the normal functioning of cells. In fact when tau becomes too phosphorylated it looses the affinity for the microtubules and detaches from them.
This fact has two major consequences. First, the phosphorylated tau, now not attached to the microtubules, forms filaments that are not soluble and tend to aggregate with each other forming ultimately what we call the fibrillary tangles.
The second consequence is that the microtubules now without the tau that acts as a stabilizer or glue loses its stability and starts wobbling and ultimately looses its function. As result of this high phosphorylation of tau and its detaching from microtubules, the communication between neurons and the transport within the neurons will suffer significantly. Both effects are considered responsible for some of the symptoms of Alzheimer's disease and other diseases of neurogenerative decline. In effect, excessive phosphorylated tau protein leads to cell death. If you would like to read more about phosphorylated tau, look at this article, available through the website of the National Library of Medicine.
It is still unclear which are the exact causes that lead to the hyperphosphorylation of tau and the following destabilization of its normal functioning. Some factors that cannot be modified include genetic risk, gender, and environmental factors. Other factors that can be modified include healthy diet, exercise, and healthy sleep and, avoidance of negative impacts like high alcohol consumption and smoking.
So how is tau protein and phosphorylated tau protein measured? To assess levels of normal or abnormal levels of tau, cerebral spinal fluid or a blood test can be used for this evaluation.
A doctor would typically indicate a need for testing if an individual is exhibiting symptoms of cognitive decline or Alzheimer's disease. Testing could allow for earlier intervention and treatment.
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Domenico Praticò, MD, holds the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research and serves as a Professor and Founding Director of the Alzheimer’s Center at Temple, as well as a Professor of Neural Sciences at Lewis Katz School of Medicine at Temple University.
For more information on the research conducted by Dr. Domenico Pratico, please visit this link.
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Stay updated with the work happening at Dr. Domenico Pratico's lab by visiting the Pratico Lab website.
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