**4. Phosphporylation of tau protein**

Protein phosphorylation is the addition of a phosphate group, by esterification, to one of three different amino acids: serine, threonine and tyrosine. Phosphorylation is the most common post-translational modification of tau described and increased tau phosphorylation reduces its affinity for microtubules leading to cytoskeletal destabilization. Eighty-five puta‐ tive phosphorylation sites on tau protein have been described in AD brain tissue (Fig. 6). The formation of fibrillar aggregates of post-translationally modified tau protein in the brain are characteristic of AD and other tauopathies. The phosphorylation of tau protein affects its solubility, localization, function, interaction with partners and susceptibility to other posttranslational modifications. However, the role of specific sites of tau phosphorylation in ear‐ ly neurodegenerative mechanisms is unknown. The molecular mechanisms of aggregation of tau into insoluble forms may help to account for the different dementias in which both clinical symptoms and age of onset differ.

**Figure 5.** tau protein, which forms part of a microtubule. The microtubule helps transpot nutrients and other impor‐ tant substances from one part of the nerve cells to another. Axon are long threadlike extensions that conduct nerve impulses away from the nerve cells; dendrites are short branched threadlike extensions that conduct nerve impulses toward the verve cell body. In Alzheimer´s disease the tau protein is abnormal and the microtubule structures col‐ lapse.
