Thioflavin T Stain: An Easier and More Sensitive Method for Amyloid Detection

Picken, Maria M.; Herrera, Guillermo A.

doi:10.1007/978-1-60761-389-3_14

Cited by 38 publications

(45 citation statements)

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“…11 Currently Congo red stain is recommended for amyloid detection by the International Society of Amyloidosis; however, other stains, in particular thioflavin, may merit consideration. 1,14 In this study, the majority of patients with amyloid in their bone marrow biopsy had evidence of systemic amyloidosis. Thus, in this series, in at least 54 of 66 cases (81%), amyloid deposits were reported in at least one other organ, predominantly in fat and kidney biopsies, whereas no data were retrievable in the remaining patients.…”

Section: Discussionmentioning

confidence: 76%

“…The majority of bone marrow pathology reports simply describe the presence or absence of amyloid deposits in the biopsy specimen and do not specify their spatial location. 10,14,[17][18][19][20][21] In rare studies, 10,14,[18][19][20][21] where the presence of amyloid deposits in the bone marrow, vessels, or stroma was described, vascular amyloid deposits were most frequently encountered.…”

Section: Discussionmentioning

confidence: 99%

“…A scoring system for bone marrow involvement in AL was previously devised in an effort to predict outcomes of bone marrow transplantation. 14,22 The following grades were included: amyloid deposits limited to the blood vessels (1þ), blood vessels with focal infiltrate into interstitium (2þ), and diffuse amyloid deposits in the bone marrow intersti- tium (3þ). By these criteria, the majority of cases in this study had a 1þ score (ie, involvement limited to the blood vessels).…”

Section: Discussionmentioning

confidence: 99%

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Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

Javidiparsijani

Picken

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Amyloidoses are rare but heterogeneous disorders for which diagnosis is contingent upon the detection of deposits by Congo red stain and amyloid protein typing determines the treatment options. Objective.— To address the reporting of bone marrow (BM) involvement by amyloid in relation to the spatial distribution of deposits and to explore whether the location of deposits may have clinical relevance. Design.— We examined 66 BM biopsies positive for amyloid with regard to the location and type of amyloid, the percentage and clonality of plasma cells, other organ involvement, and relevant clinical information. Results.— In 21 cases, amyloid deposits involved BM stroma, whereas 45 cases were nonstromal. All cases of stromal involvement were typed as AL amyloidosis (or presumed AL), whereas nonstromal involvement was associated with at least 3 types of amyloidosis: AL, ATTR, and AA. The initial diagnosis of amyloidosis was made in a BM specimen in 21 of 66 cases (31.8%). Plasma cells ranged from 1% to 80% (mean, 13.4%; median, 8%; <10% in 44 of 66 specimens [66.6%]) and were monoclonal in 58 of 66 cases (87.8%), and in 54 of 66 cases (81.8%) amyloid deposits were documented in at least one other organ. Conclusions.— This study demonstrates that there is significant heterogeneity in the spatial distribution of amyloid in BM biopsy specimens with medullary, extramedullary, purely vascular, or combined involvement. Whereas stromal deposits were associated exclusively with AL, nonstromal and purely vascular deposits were seen in at least 3 types of systemic amyloidosis (AL, AA, and ATTR). We discuss the reporting of BM biopsy tissue positivity for amyloid deposits.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

Javidiparsijani

Picken

2020

Archives of Pathology &Amp; Laboratory Medicine

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“…47 The substantial enhancement of ThT fluorescence emission and CR birefringence property makes them particularly powerful and convenient tools for amyloid detection. 33,48 Previous studies have also shown that the binding of these dyes is associated with the presence of amyloid fibrils. 33,45,46,[48][49][50] Thus, the use of ThT in conjunction with CR strongly suggests that the observed aggregates are amyloid fibrils by nature.…”

Section: Molecular and Structural Characterization Of The Mature Fibrilsmentioning

confidence: 98%

“…Bright field images and the corresponding ThT fluorescence and Congo-red birefringence images were captured using appropriate light filters on Leica DM2500 fluorescent microscope. 3,33 Fourier-transform infrared (FTIR) spectroscopy FTIR spectroscopy analysis was carried out using Bio-ATR II cell mounted on Tensor 27, Bruker FTIR instrument. 22,25,34 GNNQQNY aggregates were subjected to washing thrice by using milliQ-water and then 50 µL was loaded on to the Bio-ATR II cell.…”

Section: Nucleation Kinetics Analysesmentioning

confidence: 99%

Nucleation-dependent aggregation kinetics of YeastSup35 fragment GNNQQNY

Burra

Maina

Serpell

et al. 2020

Preprint

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An N-terminal hepta-peptide sequence of yeast prion protein Sup35 with the sequence GNNQQNY serves as an ideal model for structural understanding of amyloid assembly and kinetics. In this study, we used a reproducible solubilisation protocol that allows the generation of homogenous monomeric solution of GNNQQNY to understand the molecular details of its self-assembly mechanism. The aggregation kinetics data show that the GNNQQNY sequences follow nucleation-dependent aggregation kinetics with a critical nucleus of size ~7 monomers and that the size and efficiency of nucleation was found to be inversely related to the reaction temperature. The generated nucleus reduces the thermodynamic energy barrier by acting as a template for further self-assembly and results in highly ordered amyloid fibrils. The fibers grown at different temperatures showed similar Thioflavin T positivity, Congo red binding and β-sheet rich structures displaying a characteristic cross-β diffraction pattern. These aggregates also share morphological and structural identity with those reported earlier. The mature GNNQQNY fibers exerted no significant oxidative stress or cytotoxicity upon incubating with differentiated SHSY5Y cells. To our knowledge, this is the first study to experimentally validate previous predictions based on theoretical and molecular dynamics simulations. These findings will provide the basis for understanding the kinetics and thermodynamics of amyloid nucleation and elongation of amyloidogenic systems associated with many systemic and neurodegenerative diseases.

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Stabilization of Mineral Precursors by Intrinsically Disordered Proteins

Rao

Drechsler

Schiller

et al. 2018

Adv Funct Materials

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Biogenic nucleation and crystallization occur in confined spaces with defined interfacial properties. However, the regulatory functions of organic players in the stabilization and transport of inorganic precursors such as ion clusters, liquid-condensed phases, and amorphous particles are unclear. Given the prevalence of unstructured proteins in biogenic materials, the present study investigates the effects of biomineral-associated, intrinsically disordered protein domains with simple and repetitive amino acid compositions on mineral nucleation and their capability to form distinct supramolecular assemblies. The quantitative assessment and structural evaluation of the nucleation process reveal that disordered regions confine hydrated mineral precursors within vesicles, transiently suppressing mineral precipitation. Stabilization of the amorphous mineral is attributed to protein self-association and restructuration toward β-configurations, triggered by specific bioinorganic interactions. In consequence, the conditioned macromolecules localize at phase boundaries formed upon liquid-liquid demixing of mineral precursors and stabilize the fluidic mineral precursors against crystallization. Thus, the conformational plasticity and self-association of intrinsically disordered sequences in response to crystallization environments mediates the selection of functional macromolecular subensembles dedicated to biomaterial growth.distinct category referred to "natively denatured," "natively unfolded," or "intrinsically disordered/ unstructured proteins" (IDPs). Due to their intrinsic pliability as well as sequence characteristics of low complexity and amino acid compositional bias, [2] IDPs exhibit fascinating modes of function including induced-folding, [3] conformational adaptability toward binding sites, [4] and a unique phase behavior as hydrogels or liquid-like droplets. [1b,5] Given the recent elucidation of the contributions of IDPs in cellular homeostasis, their roles in the formation and maintenance of biomaterials also require attention.The prevalence of IDPs in the extracellular milieu is high relative to the complete cellular proteome, [6] reflecting the participation of intrinsically disordered regions (IDRs) in conditioning soft and hard extracellular matrices. The related functions of IDRs appear to encompass cell-matrix adhesion, with possible contributions in the organization and maintenance of the matrix structure. [6] Although several biomineral-associated proteins exhibit high propensities of structural disorder such as amelogenin from enamel tissue, [7] bone-associated sialoprotein and osteopontin, [8] SpSM50 from sea urchin spines, [9] Sillafins regulating biosilicification, [10] Starmarker from fish otoliths, [11] as well as AP7, Asprich, n16, PFMG1, and Shematrin from shell materials, [12] the molecular functions of IDPs in guiding mineral nucleation and crystallization are not clear. Few recent studies indicate the potential contributions of these unstructured polymers in biomineralization Mineral Nu...

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Thioflavin T Stain: An Easier and More Sensitive Method for Amyloid Detection

Cited by 38 publications

References 2 publications

Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

Nucleation-dependent aggregation kinetics of YeastSup35 fragment GNNQQNY

Stabilization of Mineral Precursors by Intrinsically Disordered Proteins

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