Tau is a neuronal microtubule-associated initially soluble cytosolic protein that promotes microtubule polymerization and bundling and is responsible for microtubule stabilization and transport of proteins in axons. Abnormal forms of it are associated with neurodegeneration.
Intracellular neurofibrillary tangles mainly composed of insoluble hyperphosphorylated aggregated tau, is the hallmark of several neurodegenerative diseases collective termed tauopathies such as Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP).
Tau accumulation can be observed in subject using a positron emission tomography (PET) imaging tracers.
Alzheimer’s disease (AD) is the most common cause of dementia and represents an economic and social disaster of massive proportions if no preventative or treatment strategies are developed.
Starting almost 20 years before the onset of symptoms, clinical AD progresses to mild impairment and then dementia of increasing levels of severity. Over time, it affects activities of daily living.
Not only does AD have a devastating impact on the quality of life for subjects and cause tremendous expense for society, but the protracted course of functional incapacity causes a terrible burden to caregivers, who are also typically elderly, and to other family members and loved ones.
Tau Pathology is Strongly Correlated with Disease Progression
Progressive Supranuclear Palsy (PSP) is a rare fatal degenerative neurological disorder; it affects about 20,000 people in the United States and has a similar occurrence rate in other parts of the world where the frequency has been examined well. PSP results in progressive impairment of balance and walking; impaired eye movement, abnormal muscle tone, speech difficulties, and problems related to swallowing and eating. Patients also frequently experience personality changes and cognitive impairment. Symptoms typically begin after age 60 but can begin earlier. The cause of PSP is unknown, and the disease is often initially misdiagnosed as Parkinson’s disease. No disease-modifying treatments have been approved for it yet. A possible genetic risk factor has been identified in two genome-wide association studies (GWAS), which causes decreased production of tauC3. This suggests that targeting tauC3 may be beneficial for treatment of PSP.
Blast-induced traumatic brain injury results from direct or indirect exposure to an explosive event as may occur in domestic or industrial accidents, terrorist attacks, or in military conflicts. While strong blasts may cause severe and acute brain injury or death, exposure to mild blast forces may result in delayed or subclinical neuropathological changes which may be more treatable. Published evidence suggests that a single blast exposure is capable of eliciting neuronal injury responses setting the stage for long-term tau pathology. A mild blast results in a rapid, and persistent, increase in tauC3. This suggests that tauC3 immunotherapy may prevent neurodegenerative processes.