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Tau proteins belong to the family of microtubule-associated proteins. They are mainly expressed in neurons where they play an important role in the assembly of tubulin monomers into microtubules to constitute the neuronal microtubules network. Microtubules are involved in maintaining the cell shape and serve as tracks for axonal transport. Tau proteins also(More)
Mutations in the genes encoding amyloid-beta precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) are known to cause early-onset, autosomal dominant Alzheimer's disease. Studies of plasma and fibroblasts from subjects with these mutations have established that they all alter amyloid beta-protein (beta APP) processing, which normally leads to(More)
OBJECTIVE To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and the different stages of AD. BACKGROUND The pathophysiologic significance of AD lesions, namely amyloid plaques and neurofibrillary tangles, is still unclear, especially their interrelationship and their link with cognitive impairment. METHODS The(More)
Tau transgenic mice are valuable models to investigate the role of tau protein in Alzheimer's disease and other tauopathies. However, motor dysfunction and dystonic posture interfering with behavioral testing are the most common undesirable effects of tau transgenic mice. Therefore, we have generated a novel mouse model (THY-Tau22) that expresses human(More)
Tau has been implicated in the organization, stabilization, and dynamics of microtubules. In Alzheimer's disease and more than 20 neurologic disorders tau missorting, hyperphosphorylation, and aggregation is a hallmark. They are collectively referred to as tauopathies. Although the impact of human tauopathies on cognitive processes has been explored in(More)
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute(More)
BACKGROUND The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the adult mammalian brain. METHODOLOGY/PRINCIPAL FINDINGS We analyzed whole genome(More)
Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested that Tau may be secreted and play a role in neural network signalling. However, once deregulated, secreted Tau may also participate in the spreading of Tau pathology in hierarchical pathways of neurodegeneration. The(More)
Recent investigations have demonstrated a local inflammatory response in Alzheimer's disease (AD), including microglia and cytokines. Levels of the cytokine tumor necrosis factor alpha (TNF-alpha) in sera from patients with AD and age-matched controls were measured by an enzyme-linked immunoassay and a cytotoxicity bioassay. Significantly elevated levels of(More)
Vasculopathy in Alzheimer's disease (AD) may represent an important pathogenetic factor of this disorder. In the present study, microvasculature was studied by immunohistochemistry using a monoclonal antibody against a vascular heparan sulfate proteoglycan. Vascular changes were consistently observed in AD and included decrease in vascular density, presence(More)