The Tau Protein

Healthy neurons have an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. A special kind of protein, tau, makes the microtubules stable. In Alzheimer's disease (AD), tau is changed chemically. It begins to pair with other threads of tau and they become tangled up together. When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells.

Excessive phosphorylation of the tau protein has been shown to be the major chemical change that causes its abnormality in AD (reference). Phosphorylation is a process that adds a phosphate group to an amino acid in a protein. The more amino acids are phosphorylated, the more likely a protein's structure will be significantly altered. An enzyme called glycogen synthase kinase 3 (GSK3) plays an important role in tau phosphorylation. Aggregated beta amyloid can activate GSK3 to phosphorylate the tau protein (reference). When both tau protein and beta amyloid were first found in AD, their cause-effect relationship was not clear. It is now confirmed that beta amyloid causes the abnormality of the tau protein, not the other way around.

Tauopathies

In studying tau and what can go wrong, investigators have found that tau abnormalities are also central to other rare neurodegenerative diseases. These diseases, called tauopathies, include frontotemporal dementia, Pick's disease, supranuclear palsy, and corticobasal degeneration. They share a number of characteristics, but also each have distinct features that set them apart from each other and from Alzheimer's disease. Characteristic signs and symptoms include changes in personality, social behavior, and language ability; difficulties in thinking and making decisions; poor coordination and balance; psychiatric symptoms; and dementia. Recent advances include the discovery of mutations in the tau gene that cause one tauopathy called frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The development of several mouse models that produce tau tangles, will allow researchers to address the many questions that remain about these diseases.

References:

National Institute on Aging, USA

Role of Tau Protein in Both Physiological and Pathological Conditions - Physiological Review, 2004.

Accumulated amyloid-beta peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer's disease. - J Alzheimers Dis., 2009.