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...

Alzheimer disease (AD) is multi-factorial and heterogeneous. Independent of the aetiology, this disease is characterized clinically by chronic and progressive dementia and histopathologically by neurofibrillary degeneration of abnormally hyperphosphorylated tau seen as intraneuronal neurofibrillary tangles, neuropil threads and dystrophic neurites, and by neuritic (senile) plaques of beta-amylo...

Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven to regulate multiple processes including nuclear translocation of Tau. In this contribution, we are a...

Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-sp...

In Alzheimer's disease (AD), a family of proteins collectively named tau are displaced from their normal association with microtubules and are found in in a hyperphosphorylated state deposited into paired helical filaments (PHFs). PHFs are the hallmark cytoskeletal pathology of the disease, and the degree of PHF pathology correlates with the clinical severity of AD. Certain apolipoprotein E (ap...

The peptide drug candidate NAP (davunetide) has demonstrated protective effects in various in vivo and in vitro models of neurodegeneration. NAP was shown to reduce tau hyperphosphorylation as well as to prevent caspase-3 activation and cytochrome-3 release from mitochondria, both characteristic of apoptotic cell death. Recent studies suggest that caspases may play a role in tau pathology. The ...

Alzheimer's disease (AD) brains are characterized by amyloid-beta-containing plaques and hyperphosphorylated tau-containing neurofibrillary tangles (NFTs); however, in frontotemporal dementia, the tau pathology manifests in the absence of overt amyloid-beta plaques. Therapeutic strategies so far have primarily been targeting amyloid-beta, although those targeting tau are only slowly beginning t...

The effects of tau hyperphosphorylation and aggregation on axonal transport were investigated in the optic nerve of mice transgenic for human mutant P301S tau. Transport was examined using cholera toxin B tracing. Retrograde transport was reduced in transgenic mice at 3 and 5 months of age, when compared to C57/Bl6 control mice. Anterograde axonal transport was also reduced in 3-month-old trans...

The aim of the present study was to investigate the relation between neurogenesis, cell cycle reactivation and neuronal death during tau pathology in a novel tau transgenic mouse line THY-Tau22 with two frontotemporal dementia with parkinsonism linked to chromosome-17 mutations in a human tau isoform. This mouse displays all Alzheimer disease features of neurodegeneration and a broad timely res...

Deposition of extracellular deposits of amyloid precursor protein (APP), tau hyperphosphorylation, neurofibrillary tangles and cholinergic deficits have been described in aged mice expressing anti-nerve growth factor (NGF) recombinant antibodies. We used antibodies recognising different phosphorylationdependent epitopes of the microtubule associated protein tau, microtubule associated-protein 2...