The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD)

Although the causative role of the accumulation of amyloid beta 1-42 (A beta 42) deposits in the pathogenesis of Alzheimer's disease (AD) has been under debate for many years, it is supposed that the toxicity soluble oligomers of Tau protein (TauOs) might be also the pathogenic factor acting on the initial stages of this disease. Therefore, we performed a thorough search for literature pertaining to our investigation via the MEDLINE/PubMed database. It was shown that soluble TauOs, especially granular forms, may be the most toxic form of this protein. Hyperphosphorylated TauOs can reduce the number of synapses by missorting into axonal compartments of neurons other than axon. Furthermore, soluble TauOs may be also responsible for seeding Tau pathology within AD brains, with probable link to A beta Os toxicity. Additionally, the concentrations of TauOs in the cerebrospinal fluid (CSF) and plasma of AD patients were higher than in non-demented controls, and revealed a negative correlation with mini-mental state examination (MMSE) scores. It was postulated that adding the measurements of TauOs to the panel of CSF biomarkers could improve the diagnosis of AD.