Disease relevance of Neurofibrillary Tangles

• Two families with Gerstmann-Sträussler-Scheinker disease (GSS) are atypical in possessing neocortical neurofibrillary tangles (NFTs), which are few or absent in other kindreds with GSS, in addition to amyloid plaques that react with prion protein (PrP) antibodies and protease-resistant PrP accumulation in the brain [1].
• Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions [2].
• Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease [3].
• Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical amyloid plaques, neurofibrillary tangles, and amyloid deposits within the walls of leptomeningeal vessels [4].
• Neuronal inclusions in the substantia nigra, termed corticobasal inclusions, were reminiscent of the globose neurofibrillary tangle of Steele-Richardson-Olszewski syndrome, and other pale inclusions resembled the pale body of Parkinson's disease, but Lewy bodies and neurofibrillary tangles were generally absent [5].

Psychiatry related information on Neurofibrillary Tangles

• Since GSK-3 also phosphorylates tau protein, the principal component of neurofibrillary tangles, inhibition of GSK-3alpha offers a new approach to reduce the formation of both amyloid plaques and neurofibrillary tangles, two pathological hallmarks of Alzheimer's disease [6].
• In Alzheimer disease (AD) the microtubule-associated protein tau is redistributed exponentially into paired helical filaments (PHFs) forming neurofibrillary tangles, which correlate with pyramidal cell destruction and dementia [7].
• Pick's disease (PiD) is characterized by the deposition of tau protein as three-repeat tau Pick bodies, whereas progressive supranuclear palsy (PSP) involves the deposition of four-repeat tau neurofibrillary tangles [8].
• Senile dementia of the Lewy body type (SDLT) can be distinguished from classical Alzheimer disease (AD) clinically by its acute presentation with confusion frequently accompanied by visual hallucinations, and neuropathologically by the presence of Lewy bodies and senile plaques (but not generally neurofibrillary tangles) in the cerebral cortex [9].

High impact information on Neurofibrillary Tangles

• The Indiana kindred variant of Gerstmann-Sträussler-Scheinker disease has amyloid plaques that contain prion protein (PrP), but is atypical because neurofibrillary tangles like those of Alzheimer disease are present [10].
• These results indicate that either APP or Abeta influences the formation of neurofibrillary tangles [11].
• The supernatants were screened for antibody activity against SDS-treated isolated neurofibrillary tangles (NFT) [12].
• Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles [13].
• The brains of individuals with Alzheimer's disease (AD) are characterized by extracellular deposition of beta-amyloid protein (Abeta), intracellular neurofibrillary tangles, and loss of neurons [14].

Chemical compound and disease context of Neurofibrillary Tangles

• Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's disease [15].
• Abeta deposition in the neuropil occurs mainly in the form of preamyloid, Congo red negative deposits, while mature neuritic plaques and neurofibrillary tangles, hallmark lesions in Alzheimer's disease (AD), are characteristically absent [16].
• Formalin-fixed, paraffin-processed sections known to contain ubiquitin-protein conjugate immunoreactivity in cortical Lewy bodies, neurofibrillary tangles, Rosenthal fibres, Pick bodies, spinal inclusions in motor neurone disease, and Mallory's hyaline in alcoholic liver disease were immunostained to localize PGP 9 [17].
• Alzheimer's disease (AD) is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal cell loss associated with membrane cholesterol release [18].
• The hierarchic order in the sequence of diffusion from the CSF into the hemispheric subpial regions and the distribution pattern of Am resemble the stereotypic topographic expansion pattern and the predominantly limbic distribution of neurofibrillary tangles (NFTs) in Alzheimer's disease and related conditions [19].

Biological context of Neurofibrillary Tangles

• Alzheimer's disease, which is characterized by amyloid plaques and neurofibrillary tangles, may be attributed to the abnormal expression of gene(s) located on human chromosome 21 [20].
• Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP [21].
• Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence [22].
• Taken together, our results suggest a novel mechanism linking amyloid deposition and neurofibrillary tangles in AD: Abeta peptides promote pathological tau filament assembly in neurons by triggering caspase cleavage of tau and generating a proteolytic product with enhanced polymerization kinetics [23].
• These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads [24].

Anatomical context of Neurofibrillary Tangles

• Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex [25].
• The filamentous brain lesions which define the disease occur within neurons (neurofibrillary tangles), in extracellular cerebral deposits (amyloid plaques) and in meningocerebral blood vessels (amyloid angiopathy) [26].
• INTERPRETATION: These results suggest that the apolipoprotein E epsilon 4 allele may influence the pattern of motor neuron loss in motor neuron disease and that it may affect neuronal function in ways unrelated to the deposition of beta-amyloid or accumulation of neurofibrillary tangles [27].
• A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain [28].
• This and other results suggest that the extracellular amyloid plaques and the intracellular neurofibrillary tangles are biochemically distinct but may result from related pathological events that originate at the level of the nerve cell and lead to its degeneration [29].

Associations of Neurofibrillary Tangles with chemical compounds

• Antigenic changes similar to those seen in neurofibrillary tangles are elicited by glutamate and Ca2+ influx in cultured hippocampal neurons [30].
• We identified the multiphosphorylation domain of the rat heaviest NF subunit--tandem repeats of Lys-Ser-Pro-Xaa (where Xaa is a small uncharged amino acid and serine is phosphorylated)--as the determinant recognized by 15 of the 16 mAbs from this collection of greater than 500 mAbs that detected neurofibrillary tangles [31].
• Specifically, antibodies against two Maillard end products, pyrraline and pentosidine, immunocytochemically label neurofibrillary tangles and senile plaques in brain tissue from patients with Alzheimer disease [32].
• Sections hybridized with the tau probe and then double-labeled with thioflavine S revealed that neurons containing neurofibrillary tangles continue to synthesize tau protein [33].
• Animals examined at 85 and 100 days after injection of aluminum chloride had fewer neurofibrillary tangles of none at all, and apparently they had recovered from the neurofibrillary changes [34].

Gene context of Neurofibrillary Tangles

• Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing a C-terminal fragment of human amyloid precursor protein [35].
• In situ hybridization localized expression to pyramidal neurons in the cerebral cortex, the same population that contains neurofibrillary tangles and high levels of immunoreactive PTP [36].
• Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated protein tau [37].
• Apolipoprotein E (apoE), a plasma apolipoprotein that plays a central role in lipoprotein metabolism, is localized in the senile plaques, congophilic angiopathy, and neurofibrillary tangles of Alzheimer disease [38].
• Neurofibrillary tangles similar to those in Alzheimer's disease have been reported in most juvenile/adult patients without amyloid beta protein (Abeta) deposits [39].

Analytical, diagnostic and therapeutic context of Neurofibrillary Tangles

• Glutamate-, glutaminase-, and taurine-stained neurons were found to contain neurofibrillary tangles using either double immunofluorescence with tau antisera, double immunoperoxidase stains, or silver and thioflavine S counterstains [40].
• However, when the same specimens were subjected to Western blotting, many cases with or without neurofibrillary tangles showed some accumulation of SDS-stable Abeta dimers that cannot be detected by EIA [41].
• Several cellular changes have been identified that are related to amyloid beta plaques and neurofibrillary tangles found in the autopsied brains of AD patients and in AD animal models [42].
• By immunocytochemistry, we first colocalized the presence of IB1/JIP-1 with JNK and phosphorylated tau in neurofibrillary tangles [43].
• Antibody SMI33 recognizes neurofibrillary tangles after treatment with alkaline phosphatase, suggesting that the proline-directed protein kinase may phosphorylate tau at sites that are phosphorylated in Alzheimer's disease [44].

References