Review: Tau in biofluids – relation to pathology, imaging and clinical features

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In 1986, one year after the sequencing of amyloid β (Aβ) in senile plaques in Alzheimer's disease (AD) brains 1, data were published showing that neurofibrillary tangles (the other major neuropathological hallmark of AD) are composed of abnormally phosphorylated and truncated forms of tau 2. Tau is a microtubule‐binding axonal protein that promotes microtubule assembly and stability 4. Abnormal phosphorylation and truncation of tau may lead to disassembly of microtubules and impaired axonal transport with compromised neuronal function and tau aggregation into paired helical filaments and neurofibrillary tangles 5. Apart from executing important intracellular functions, tau is normally secreted from neurons into the brain interstitial fluid 6. This fluid communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner that is regulated by the glymphatic clearance system of the brain, with blood, where tau may be enzymatically degraded and cleared from the body by unknown mechanisms. Several methods to measure total tau (T‐tau) and phospho‐tau (P‐tau) in CSF have been developed. They are reviewed in detail below and their utility in differential diagnostics of neurodegenerative diseases is summarised in Table 1.
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