Abnormal tau aggregation is a pathological hallmark of many neurodegenerative disorders and it is becoming apparent that soluble tau aggregates play a key role in neurodegeneration and memory impairment. Despite this pathological importance, there is currently no single method that allows monitoring soluble tau species in living cells. In this regard, we developed a cell-based sensor that visua...

Hyperphosphorylated tau proteins accumulate in the paired helical filaments of neurofibrillary tangles seen in such tauopathies as Alzheimer's disease. In the present paper we show that tau turnover is dependent on degradation by the proteasome (inhibited by MG132) in HT22 neuronal cells. Recombinant human tau was rapidly degraded by the 20 S proteasome in vitro, but tau phosphorylation by GSK3...

In normal adult brain the microtubule associated protein (MAP) tau contains 2-3 phosphates per mol of the protein and at this level of phosphorylation it is a soluble cytosolic protein. The normal brain tau interacts with tubulin and promotes its assembly into microtubules and stabilizes these fibrils. In Alzheimer disease (AD) brain tau is three to fourfold hyperphosphorylated. The abnormally ...

Aggregation and increased phosphorylation of tau at selected sites ("hyperphosphorylation") are histopathological hallmarks of Alzheimer's disease (AD). However, it is not known whether the tau pathology has a primary role during neuronal degeneration. To determine the role of tau hyperphosphorylation in AD, pseudohyperphosphorylated tau (PHP-tau) that simulates disease-like permanent, high sto...

Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathol...

Protein tau-3R/4R isoform ratio and phosphorylation regulates binding to microtubules and, when disturbed by aging or mutations, results in diverse tauopathies and in neurodegeneration. The underlying mechanisms were studied here in three transgenic mouse strains with identical genetic background, all expressing the tau-4R/2N isoform driven specifically in neurons by the thy1 gene promoter. Two...

This Fifth International WEIN Symposium is devoted to physics beyond the standard model. This talk is about tau lepton physics, but I begin with the question: do we know how to nd new physics in the world of elementary par-ticles? This question is interwoven with the various tau physics topics. These topics are: searching for unexpected tau decay modes; searching for additional tau decay mechan...

Recent evidence suggests that tau aggregates are not only neurotoxic, but also propagate in neurons acting as a seed for native tau aggregation. Prion-like tau transmission is now considered as an important pathogenic mechanism driving the progression of tau pathology in the brain. However, prion-like tau species have not been clearly characterized. To identify infectious tau conformers, here w...

$\mbox{CP}$-odd asymmetries in the processes $e^+e^-\rightarrow \tau^+\pi^-\nu_\tau$, \pi^+\tau^-\bar\nu_ \tau$, \tau^+\rho^-\nu_\tau$, \rho^+\tau^-\bar\nu_\tau $, $e^+e^-\to \tau^+e^-\nu_\tau{\bar\nu}_e\,,\,$ and $\,e^+e^-\to \tau^-e^+\nu_e{\bar\nu}_\tau$ are investigated with account for longitudinal polarization of electron (or positron) beam. These is a manifestation electric dipole form fa...

Tau aggregation is a hallmark of several neurodegenerative diseases, including AD (Alzheimer's disease), although the mechanism underlying tau aggregation remains unclear. Recent studies show that the proteolysis of tau plays an important role in both tau aggregation and neurodegeneration. On one hand, truncation of tau may generate amyloidogenic tau fragments that initiate the aggregation of t...