Formation of Tau Oligomers in Disease

In the normal central nervous system tau protein is found mostly in axons, the long processes that conduct impulses to other neurons, where it modulates the length and stability of microtubules necessary for signaling between neurons. During disease tau dissociates from microtubules leading to their disintegration. There are 20 known tauopathies where Alzheimer’s disease and frontotemporal dementia are the most prevalent.

Figure 1 – Tau function in healthy neuron

Figure 2 – Tau aggregation in disease

Multiple disease-related events such as brain injury and oxidative stress can activate pathways leading to this modification of tau protein. Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive traumatic brain injury experienced in military combat and sports – such as boxing, and football.

The accumulation of tau oligomers in disease is associated with neuronal loss and memory impairment, whereas the tangles form later in disease and may have a protective function in sequestering the neurotoxic oligomers.