Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paired helical filament (PHF)/tau immunoreactive dystrophic neurites are a common pathological feature in the brain of patients with Alzheimer's disease. Recent studies suggest that swollen neurofilament-immunoreactive neurites are also present in senile plaques. In the present study, we investigated whether PHF/tau-positive dystrophic neurites are located in all subtypes of plaques and whether swollen neurofilament-immunoreactive neurites are hyper-phosphorylated, using a battery of antibodies to PHF/tau, neurofilament, and beta-amyloid protein. PHF/tau-positive dystrophic neurites were present in and around nearly all subtypes of plaques, including small amyloid deposits, diffuse plaques, and perivascular plaques in the hippocampal formation of Alzheimer brain. The earlier changes were detectable with AT8 antibody and later changes with PHF-1 antibody. Plaque-associated PHF/tau-positive dystrophic neurites were rare or absent in the hippocampal formation of normal aged brain. Swollen neurofilament-positive neurites appeared to be hyper-phosphorylated in Alzheimer's disease and to a lesser degree in aged control brains. Neurites that contained hyper-phosphorylated tau as well as neurofilament were strongly argentophilic because both populations of dystrophic neurites stained with silver stains. Swollen neurofilament-positive plaque-associated neurites were often present in the absence of PHF/tau-positive plaque-associated dystrophic neurites. These data suggest that PHF/tau-positive dystrophic neurites are a common component of all subtypes of plaques in Alzheimer brain and neurofilament protein in swollen neurites, like tau protein, is hyper-phosphorylated. Hyper-phosphorylated neurofilaments in plaque-associated neurites may represent one of the earliest cytoskeletal changes in vulnerable neurons in Alzheimer's disease and aged control brains.
 ...
PMID:Plaque biogenesis in brain aging and Alzheimer's disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments. 895 27

We describe a computer application, "BioVision", that can be trained to quickly and effectively classify and quantify user definable histological objects (e.g., senile plaques, neurofibrillary tangles) within single or double-labeled immunocytochemically stained sections. For a given image population, BioVision is interactively trained (in Independent User Mode) by an investigator to perform the desired classifications. This training yields a statistical model of the different types of objects occurring in the target image population. The resulting model can then be used (in Automated User Mode) to classify all objects in any image or images from the target population. BioVision simplifies the quantification of complex visual objects and improves inter-rater reliability. The program accomplishes classification in two major stages: pixel classification and blob classification. In pixel classification, each pixel is assigned to one of some number of substance classes, based on its chromatic properties and local context, reflecting basic histological distinctions of interest. In the blob classification phase, the image's pixels are first partitioned into "blobs": maximal connected sets of pixels assigned to the same substance class. Then, based on its size, shape, textural and contextual properties, each blob is assigned to a histological object class. A Bayesian classifier is used in each of the pixel and blob classification stages. We report several tests of BioVision. First, we applied BioVision to classify senile plaques and neurofibrillary tangles in several test cases of Alzheimer's brain immunostained for beta-amyloid and PHF-tau and compared the results to those produced by experienced investigators. BioVision was trained to classify Plaque-type blobs as either plaques or plaque-type nonentities, and tangle-type blobs as either tangles or tangle-type nonentities. BioVision classified the objects with an accuracy comparable to the trained investigator. Next, we applied BioVision to the task of counting all the tangles in hippocampal images from 22 Alzheimer's disease (AD) cases selected to span a broad range of dementia levels from the tissue repository of UC Irvine's Center for the study of Brain Aging and Dementia. The tangle counts produced by BioVision proved to be significantly better predictors of the cases' adjusted MMSE scores than any of tangle load, age at death, post mortem interval or the interval between the last MMSE score and death.
 ...
PMID:BioVision: an application for the automated image analysis of histological sections. 1627 3

A central issue in the pathogenesis of tauopathy is the question of how tau protein dysfunction leads to neurodegeneration. We have previously demonstrated that the absence of tau protein is associated with destabilization of microtubules and impaired neurite outgrowth (Dawson et al., 2001; Rapoport et al., 2002). We now hypothesize that the absence of functional tau protein may render the central nervous system more vulnerable to secondary insults such as the overexpression of mutated beta amyloid precursor protein (APP) and traumatic brain injury. We therefore crossed tau knockout mice (Dawson et al., 2001) to mice overexpressing a mutated human APP (APP(670,671), A(sw)) (Hsiao et al., 1996) and created a mouse model (A(sw)/mTau(-/-)) that provides evidence that the loss of tau function causes degeneration of neuronal processes. The overexpression of APP(670,671) in tau knockout mice, elicits the extensive formation of axonal spheroids. While spheroids are only found associated with Abeta plaques in mice expressing APP(670,671) on an endogenous mouse tau background (Irizarry et al., 1997), A(sw)/mTau(-/-) mice have spheroids not only surrounding Abeta plaques but also in white matter tracks and in the neuropil. Plaque associated and neuropil dystrophic neurites and spheroids are prominent features of Alzheimer's disease (Masliah et al., 1993; Terry, 1996; Stokin et al., 2005), and our current data suggests that loss of tau function may lead to neurodegeneration.
 ...
PMID:Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease. 2043 28