Tau, a microtubule associated protein, aggregates into intracellular paired helical filaments (PHFs) by an unknown mechanism in Alzheimer's disease (AD) and other tauopathies. A contributing factor may be a failure to metabolize free cytosolic tau within the neuron. The buildup of tau may then drive the aggregation process through mass action. Therefore, proteases that normally degrade tau are ...

Hyperphosphorylation and deposition of tau into neurofibrillary tangles is a hallmark of Alzheimer disease (AD). Alternative splicing of tau exon 10 generates tau isoforms containing three or four microtubule binding repeats (3R-tau and 4R-tau), which are equally expressed in adult human brain. Dysregulation of exon 10 causes neurofibrillary degeneration. Here, we report that cyclic AMP-depende...

Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer's disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into toxic tau species in AD brains. To prevent the cascade of events leading to ne...

From electron-positron collision data collected with the CLEO detector operating at Cornell Electron Storage Ring near sqrt[s]=10.6 GeV, improved measurements of the branching fractions for tau decays into three explicitly identified hadrons and a neutrino are presented as B(tau(-)-->pi(-)pi(+)pi(-)nu(tau))=(9.13+/-0.05+/-0.46)%, B(tau(-)-->K-pi(+)pi(-)nu(tau))=(3.84+/-0.14+/-0.38) x 10(-3), B(...

Recent studies have demonstrated that human tau can be secreted by neurons and non-neuronal cells, an event linked to the propagation of tau pathology in the brain. In the present study, we confirmed that under physiological conditions, one tau-positive band was detected in the culture medium with an anti-tau antibody recognizing total tau and the Tau-1 antibody directed against unphosphorylate...

Abnormal alternative splicing of tau exon 10 results in imbalance of 3R-tau and 4R-tau expression, which is sufficient to cause neurofibrillary degeneration. Splicing factor SC35, a member of the superfamily of the serine/arginine-rich (SR) proteins, promotes tau exon 10 inclusion. The molecular mechanism by which SC35 participates in tau exon 10 splicing remains elusive. In the present study, ...

The pathological hallmarks of Alzheimer’s disease (AD) are extracellular β-amyloid deposition and intracellular tau inclusions. While β-amyloid deposition does not correlate with clinical progression of AD, the diffusion of neurofibrillary tangles (NFTs) from the entorhinal cortex to the neocortex, followed by neuronal and synapse loss, matches well with the clinical progression of AD symptomat...

Characteristic tau isoform composition of the insoluble fibrillar tau inclusions define tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal dementia with parkinsonism linked to chromosome 17/frontotemporal lobar degeneration-tau (FTDP-17/FTLD-tau). Exon 10 splicing mutations in the tau gene, MAPT, in familial FTDP-17 cause elevation of tau is...