Tau as a Biomarker of Neurodegeneration

Abstract

Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological advances that have catapulted tau from obscurity to the forefront of biomarker diagnostics. Comprehensive updates are provided describing the burgeoning clinical applications of tau as a biomarker of neurodegeneration. For the clinician, tau not only enhances diagnostic accuracy, but holds promise as a predictor of clinical progression, phenotype, and response to drug therapy. For patients living with neurodegenerative disorders, characterization of tau dysregulation could provide much-needed clarity to a notoriously murky diagnostic landscape.

Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools

“…It has the potential for multiple phosphorylation at Serine (S), Threonine (T), and Proline (P) residues within its Proline-rich region (PRG) or C-terminal region (CTR), and only 2–3 residues are phosphorylated in the healthy brain. However, there are around five to nine moles of phosphate per mole of tau in AD and other tauopathies ( Grundke-Iqbal et al, 1986 ; Kopke et al, 1993 ; Holper et al, 2022 ). Hyperphosphorylation of Tau is associated with an aggregation of multimers and fibers ( Despres et al, 2017 ) that seem to mediate cognitive defects.…”

Diagnostic challenges for dementia in Australia: are blood‐based biomarkers the solution?

“…Measurement of blood p-tau181 and p-tau217 using Simoa correlates well with clinical and imaging features of Alzheimer's disease, such as hippocampal atrophy on MRI, and differentiates it from other neurodegenerative disorders, including frontotemporal dementia. 16 P-tau217 levels may even indicate Alzheimer's pathology before changes develop on tau-PET; therefore, it may be a useful marker of early disease. 17 Regarding Lewy body dementias, attempts at measuring CSF and blood α-synuclein to aid diagnosis have so far failed to produce reliable results.…”

Posttranscriptional regulation of neurofilament proteins and tau in health and disease

“…Moreover, deletion of neurofilament proteins resulted in a dramatic decrease in the total number of tau-positive spheroids and attenuated neurodegenerative disease phenotype in these mice, suggesting a role for neurofilament proteins in the pathogenesis of neurofibrillary tau lesions in neurodegenerative disorders ( Ishihara et al, 2001 ). Recently, neurofilament ( Yuan and Nixon, 2021 ) and tau proteins ( Holper et al, 2022 ) have been used together as biomarkers of neuronal integrity reflecting the magnitude of neuronal injury and neurodegeneration.…”