The microtubule-associated protein Tau is a major component of the neurofibrillary tangles that serve as a neuropathological hallmark of Alzheimer's disease. Tau is a substrate for protein phosphorylation at multiple sites and occurs in tangles in a hyperphosphorylated state. However, the physiological functions of Tau phosphorylation or how it may contribute mechanistically to Alzheimer's pathophysiology are not completely understood. Here, we examined the function of human Tau phosphorylation at three sites, Ser199, Ser202, and Thr205, which together comprise the AT8 sites that mark abnormal phosphorylation in Alzheimer's disease. Overexpression of wild-type Tau or mutated forms in which these sites had been changed to either unphosphorylatable alanines or phosphomimetic aspartates inhibited mitochondrial movement in the neurite processes of PC12 cells as well as the axons of mouse brain cortical neurons. However, the greatest effects on mitochondrial translocation were induced by phosphomimetic mutations. These mutations also caused expansion of the space between microtubules in cultured cells when membrane tension was reduced by disrupting actin filaments. Thus, Tau phosphorylation at the AT8 sites may have meaningful effects on mitochondrial movement, likely by controlling microtubule spacing. Hyperphosphorylation of the AT8 sites may contribute to axonal degeneration by disrupting mitochondrial transport in Alzheimer's disease.

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Tau protein plays a crucial role in diagnosing neurodegenerative diseases. However, the assay employed to detect tau protein on a nanoscale is a great challenge for the early diagnosis of diseases. ELISA, western-blotting, and molecular-based methods such as PCR and Real-time PCR are the most widely used methods for detecting tau protein. Such methods are subject to certain limitations: the need for advanced equipment, low sensitivity, and specificity, to name a few. Accordingly, the necessity of discovering advanced and novel methods for monitoring tau protein becomes highlighted. Biosensors are one of the remarkable methods considered by researchers that can largely eliminate the problems and limitations associated with routine methods. The main objective of the present study was to review the latest biosensors developed to detect the tau protein. Further, the problems and limitations of routine diagnosis methods were discussed in detail.

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