Disease relevance of THIOFLAVIN

• We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar Abeta deposits in both AD and PSAPP mice [1].
• The geometry of the hearts and ischemic zones was preserved, the margins of ischemia being defined as the outer border of Thioflavin S nonfluorescence [2].
• In the current study, we used BSB to probe postmortem tissues from patients with various neurodegenerative diseases with diagnostic lesions characterized by fibrillar intra- or extracellular lesions and compared these results with standard histochemical dyes such as thioflavin S and immunohistochemical stains specific for the same lesions [3].
• In five groups of anesthetized, open-chest rabbits (30-min coronary occlusion and different durations of reperfusion), anatomic no reflow was determined by injection of thioflavin S at the end of reperfusion and compared with regional myocardial blood flow (RMBF; radioactive microspheres) and infarct size (triphenyltetrazolium) [4].
• Transgenic mice overexpressing TGF-beta1 in astrocytes develop AD-like cerebrovascular abnormalities, including perivascular astrocytosis, microvascular basement membrane thickening, and accumulation of thioflavin S-positive amyloid in the absence of parenchymal degeneration [5].

Psychiatry related information on THIOFLAVIN

• In a study of 32 brains obtained from patients with Alzheimer's disease (AD), thioflavin S-stained sections from the PAG contained major pathological changes in 81% of cases [6].

High impact information on THIOFLAVIN

• A subset of these deposits also bind the amyloid-specific dye thioflavin S, indicating that these deposits have the tinctural characteristics of classic amyloid [7].
• The synthetic PHFs bound the dye thioflavin S used in Alzheimer disease diagnostics [8].
• Severe depression of regional blood flow during reperfusion was present within the infarcted tissue and was associated with an anatomic perfusion defect as defined by thioflavin S; there was moderate depression of flow within the noninfarcted, salvaged subepicardium [9].
• Propranolol also limited microvascular injury so that perfusion defects, detected with the dye thioflavin S, were smaller in treated dogs [10].
• Of the 20 samples from Nairobi, 3 (15%) brains exhibited neocortical A beta deposits that varied from numerous diffuse to highly localized compact or neuritic plaques, many of which were also thioflavin S positive [11].

Chemical compound and disease context of THIOFLAVIN

• Neuritic plaques (NPs), neurofibrillary tangles (NFTs) and congophilic angiopathy (CA), the three characteristic lesions in Alzheimer's disease, are easily detected in paraffin sections using light microscopy and specific staining methods including Congo red and Thioflavin S [12].

Biological context of THIOFLAVIN

• Thioflavin S histochemistry suggested accumulations of amyloid in the cerebrovasculature of transgenic mice with the highest expression of the beta APP-C100 transgene [13].
• Actinomycin D, but not a caspase inhibitor, prevented inclusion formation, whereas both agents inhibited cell death. alpha-Synuclein and thioflavin S staining were found within the inclusions. alpha-Synuclein, however, did not appear to be ubiquitinated or aggregated [14].
• Studies of the interaction of these complexes and of the dyes with the pBR322 plasmid superhelical DNA demonstrated that while each complex and dye readily associated with the DNA in a dose-dependent manner, only Pt(Thioflavin)2 and Thioflavin produced irreversible DNA changes (single-strand breaks) [15].

Anatomical context of THIOFLAVIN

• Various areas of ischemia were produced by occluding large and small coronary artery branches, and the resultant changes in ischemic shape were delineated with Thioflavin S injections and postmortem ultraviolet photography [16].
• Some neurofilament-positive neurites were not visualized with thioflavin, but almost all tau-positive neurites were colabeled with thioflavin [17].
• At the light microscopy level, most tau was found with microtubules, or diffusely distributed in the cytoplasm, but none of this appeared thioflavin S-positive [18].
• The perinuclear inclusion bodies, but not the small cytoplasmic aggregates, were thioflavin S-positive, suggesting the amyloid-like conformation [19].
• In AD and DS cerebral cortex, CLAC invariably colocalized with Abeta42 but often lacked Abeta40- or thioflavin S (thioS)-reactivities [20].

Associations of THIOFLAVIN with other chemical compounds

• Histochemical staining of adjacent sections with Bielschowsky's silver impregnation and with Congo red or thioflavin S-staining techniques was also done to identify the structures with amyloid deposition [21].
• The results were obtained using a thioflavin S fluorescence assay for the detection and quantification of tau aggregation in solution, a tryptophan fluorescence assay using tryptophan-containing mutants of tau, and confirmed by a pelleting assay and electron microscopy of the products [22].
• These eosinophilic inclusions share many characteristics with Lewy bodies, including a core and halo organization, immunoreactivity to ubiquitin, alpha-synuclein, synphilin-1, Parkin, molecular chaperones, and proteasome subunit as well as staining of some with thioflavin S [23].
• After 4 h of reperfusion, infarct size and no reflow zone were measured postmortem by triphenyltetrazolium and thioflavin staining, respectively [24].
• On the basis of circular dichroism spectroscopy and reactivity with thioflavin S and 8-anilino-1-naphthalenesulfonic acid fluorescent probes, the inducer stabilized a monomeric species with the folding characteristics of a premolten globule state [25].

Gene context of THIOFLAVIN

• The measures of Abeta deposition, Abeta-immunoreactive plaques with and without cores, thioflavin histofluorescent plaques, and concentrations of insoluble Abeta, failed to distinguish HPC from AD patients and were poor correlates of synaptic change [26].
• Also, SAP and C1q enhanced PrP-peptide fibril formation as revealed by electron microscopy and thioflavin S-based quantitative assays [27].
• Neuritic plaques identified on double label experiments with thioflavin include somatostatin axons but not neurons [28].
• Amyloid burden, expressed as the percentage area occupied by thioflavin S-positive amyloid deposits, increased an average of 179-fold from 12 to 54 weeks of age (0.02+/-0.01% to 3.57+/-0.29%, mean+/-S.E.M., respectively) in five regions of the cortex and two of the hippocampus [29].
• Electron microscopy and thioflavin S reactivity of the fractions show that the juxtanuclear inclusion bodies are filled with amyloid-like alpha-synuclein fibrils, whereas both the small aggregate fractions contain non-fibrillar spherical aggregates with distinct size distributions [30].

Analytical, diagnostic and therapeutic context of THIOFLAVIN

• The area of impaired perfusion (absent thioflavin) averaged 9.5 +/- 3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 +/- 8.2% of the risk region, p less than 0.05) [31].
• The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2+/-1.8%, 6.7+/-4.4%, and 9.9+/-3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P<0.03) and correlated well with microvascular obstruction (MBF <50% of remote region, r=0.99 and thioflavin S, r=0.93) [32].
• The filamentous nature of these thioflavin-binding amyloid polymers was verified by electron microscopy [33].
• The histopathology of senile plaques was studied using double-labeling immunohistochemistry and lectin histochemistry with thioflavin S fluorescent microscopy in 9 cases of Alzheimer's disease, 2 nondemented elderly individuals, and 3 individuals with non-Alzheimer primary degenerative dementias [17].
• The severity of ischemia was determined by the radioactive microsphere and thioflavin S techniques [34].

References