Abnormal phosphorylation of the microtubule associated protein tau component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) may result from alterations in protein kinase expression.
The tau protein is a component of paired helical filaments which accumulate in degenerating neurons in the brain of patients with AD and with less intensity of normal elderly individuals.
The microtubule-associated protein tau is present in the pathologic hallmarks of Alzheimer's disease and its production and deposition have been implicated in the pathogenesis of the disease.
Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease.
The present data extend earlier findings of abnormal processing of neurofilaments and tau protein in Alzheimer disease and, together with reported abnormal processing of cerebrovascular amyloid beta-protein, suggest that inhibition of the processing of multiple proteins is basic to the pathogenesis of Alzheimer disease, whereas formation of plaques and tangles could be merely the most striking histologic result.
The proof that at least part of tau protein forms a component of the paired helical filament core opens the way to understanding the mode of formation of paired helical filaments and thus, ultimately, the pathogenesis of Alzheimer disease.
A central event in Alzheimer's disease is the conformational change from normally circulating soluble amyloid beta peptides (A beta) and tau proteins into amyloid fibrils, in the form of senile plaques and neurofibrillary tangles respectively.
We conclude that abnormal tau protein in CBD comprises the entire tau molecule and is highly phosphorylated, but is distinguished from AD and PSP by the paucity of epitopes contained in the alternatively spliced exon 3.
Cerebrospinal fluid from 70 patients with Alzheimer's disease (AD) and 96 patients with non-AD neurological diseases as well as 19 normal control subjects was surveyed by sandwich enzyme-linked immunosorbent assay to quantitate levels of the microtubule-associated protein tau in cerebrospinal fluid.
These data provide insight into how PHF-tau disturbs neuronal function, and add to a growing body of evidence that oxidant stress contributes to the pathogenesis of AD.
We conclude that transgenic human tau protein showed pre-tangle changes similar to those that precede the full neurofibrillary pathology in Alzheimer's disease.
Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of beta-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala.
The two major neuropathological hallmarks of Alzheimer's disease (AD) are extracellular senile plaques, the principal component of which is the A beta amyloid peptide, and intraneuronal neurofibrillary tangles, which are composed of aggregated tau protein in the form of paired helical filaments (PHF).
Using monospecific antibody to AGEs, we have colocalized these AGEs with paired helical filament tau in neurofibrillary tangles in sporadic Alzheimer disease.
They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease.
Alzheimer's disease (AD) is characterised neuropathologically by the presence of abundant extracellular beta-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau.
The concentration of tau protein is elevated in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), suggesting that CSF tau may be a useful biochemical diagnostic marker for this disorder.