What are Tau protein? and it’s relationship with Alzheimer’s disease

Tau protein is often linked with Alzheimer’s in virtually all medical textbooks. Often think tau protein is found in Alzheimer’s disease. This statement is not wrong, in facts, tau protein is found in every individual; not only those with brain disease. So, what is tau protein?

Tau protein is brain microtubule–associated protein (although it is found in other cells of the body, but it is more in the brain; specifically the frontal and temporal lobe). It is a intracellular protein, with function to assemble and stabilised the microtubules that transport cell organelles, glycoprotein and other important material throughout the cells. Therefore, any abnormality of tau protein, could disrupt such process, any result in abnormal neuron function, and degeneration.

What more is known about tau protein? Tau protein is encoded by Tau/MAPT gene in the long arm of chromosome 17 at band position 17q21. After translation of the gene into mRNA, followed by splicing which can result in the appearance of six tau isoforms. The tau isoforms can be further modified, mainly by phosphorylation, making additional tau isoforms. The balance of tau phosphorylation is important, aberrant hyperphosphorylation of tau protein can cause neurodegeneration. Alonso et. al. 1996 stated that a possible explanation that tau toxicity is based on the fact that phosphorylated tau can recruit unmodified tau (and other MAPs) from microtubules, which may result in disruption of microtubules.

In Alzheimer’s disease, there is presence of neurofibrillary tangle (NFT) in the brain histopathology. Neurofibrillary tangles are made up of paired helical filaments formed by hyperphosphorylated tau. Hyperphosphorylated tau is strongly correlated with Alzheimer’s disease. How NFT is formed in Alzheimer’s disease is not fully understood, but many genetic role has been implicated.

Finally, tau protein is normally found in healthy individual, but abnormal hyperphosphorylated tau could result in neuron death, thus neurodegeneration. It is important to noted that abnormal hyperphosphorylated tau is not only found in Alzheimer’s disease, but also in other neurodegenerative diseases such as frontotemporal lobe dementia, corticobasal degeneration, ect. Also, in Alzheimer’s, tau is not the only abnormal protein aggregation; for instances, misfolded beta amyloid 42 protein is strongly linked as well.

References

1. Cytoskeleton of the Nervous System (Advance in Neurobiology 3)

2. Harrison’s Internal Medicine 18th edition

3. http://www.ncbi.nlm.nih.gov/pubmed/10967355

4. http://www.nature.com/ng/journal/v25/n4/pdf/ng0800_402.pdf

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