Tau pathology: predictive diagnostics, targeted preventive and personalized medicine and application of advanced research in medical practice

Abstract

Microtubules are key cytoskeletal elements found in all eukaryotic cells. The microtubule shaft is composed of the heterodimer protein, tubulin and decorated with multiple microtubule associated protein, regulating microtubule function. Tau (tubulin associated unit) or MAPT (microtubule associated protein tau), among the first microtubule associated proteins to be identified, was implicated in microtubule initiation as well as assembly, with increased expression in neurons and specific association with axonal microtubules. Alzheimer’s disease (AD) is the most prevalent tauopathy, exhibiting tau-neurofibrillary tangles associated with cognitive dysfunction. AD is also characterized by β-amyloid plaques. An abundance of tau inclusions, in the absence of β-amyloid deposits, can be found in Pick’s disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases, collectively described as tauopathies. The increase in tau pathology in AD correlates with the associated cognitive decline. The current manuscript touches on the variability as well as common denominators of the various tau pathologies coupled to new approaches/current innovation in treatment of tauopathies in favor of advanced technologies in predictive diagnostics, targeted preventive and personalized medicine (PPPM).

Tau Protein in Biological Fluids and Its Clinical Value

“…Tau (τ = tubulin-associated unit) protein je jeden z neurocytoskeletálních proteinů, který se uplatňuje v patogenezi závažných neurologických onemocnění. Byl popsán v roce 1975 jako protein, který navozuje vytváření mikrotubulů 1,2 .…”

Neurodegeneration: accelerated ageing or inadequate healthcare?

“…As reviewed by I. Grossman et al [ 24 ], the AD-dedicated research programmes are essential to validate currently available biomarkers for their clinical utility in supporting targeted preventive measures, paving the road for rational health management and ensuring innovative reimbursement programmes developed by policy-makers. In terms of targeted neuroprotection, current particular interest is focused on several forms of taupathies and TAU-protein related drugs to break the potentially toxic aggregates, inhibiting phosphorylation, accelerating dephosphorylation of TAU-protein and related microtubule interaction as reviewed by I. Gozes [ 25 ].…”

Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer’s Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways

“…With advances in high-throughput sequencing and microarray technology, bioinformatics analysis is cumulatively employed to investigate genetic factors that contribute to the risk of AD [ 8 ]. Several AD-related genes (e.g., PP2A, RGS2, TOMM40, and APOE4) have been recognized as potential candidates in an attempt to predict individual susceptibility, provide targeted prevention, and create personalized treatment [ 9 – 11 ]. Nevertheless, integrated genomic analysis has not been systematically applied to AD research [ 12 ].…”