Thioflavin S fluorescent and congo red anisotropic stainings in the histologic demonstration of amyloid

Kelényi, G

doi:10.1007/bf00688089

Cited by 101 publications

(58 citation statements)

References 20 publications

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“…1 AI) and apple-green birefringence (Fig. 1 AII), punctuated by a dark cross of extinction, indicating a radially ordered spherical body (1,18). These features are reiterated in the orientation images of LB (Fig.…”

Section: Resultsmentioning

confidence: 80%

Imaging linear birefringence and dichroism in cerebral amyloid pathologies

Jin

Claborn

Kurimoto

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

187

149

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New advances in polarized light microscopy were used to image Congo red-stained cerebral amyloidosis in sharp relief. The rotating-polarizer method was used to separate the optical effects of transmission, linear birefringence, extinction, linear dichroism, and orientation of the electric dipole transition moments and to display them as false-color maps. These effects are typically convolved in an ordinary polarized light microscope. In this way, we show that the amyloid deposits in Alzheimer's disease plaques contain structurally disordered centers, providing clues to mechanisms of crystallization of amyloid in vivo. Comparisons are made with plaques from tissues of subjects having Down's syndrome and a prion disease. In plaques characteristic of each disease, the Congo red molecules are oriented radially. The optical orientation in amyloid deposited in blood vessels from subjects having cerebral amyloid angiopathy was 90°out of phase from that in the plaques, suggesting that the fibrils run tangentially with respect to the circumference of the blood vessels. Our result supports an early model in which Congo red molecules are aligned along the long fiber axis and is in contrast to the most recent binding models that are based on computation. This investigation illustrates that the latest methods for the optical analysis of heterogeneous substances are useful for in situ study of amyloid.T he abnormal transformation of proteins to amyloid fibrils is closely related to the so-called conformational diseases that include the common neurodegenerative disorders such as Alzheimer's disease (AD) and prion diseases. The kinetic and structural bases of fibrillogenesis in these diseases are as yet undetermined. Nevertheless, the presence of amyloid in diseased tissues has been used for the purpose of pathological diagnosis and construction of theories of pathogenesis. A structural characterization and categorization of various forms of amyloid aid accurate diagnosis of amyloid disorders and further our mechanistic understanding of an increasing list of conformational diseases.The principal diagnostic criterion of amyloidosis, established by Divry and Florkin (1), is the detection with a polarizing optical microscope of so-called apple-green birefringence (2-6) from Congo red (CR)-stained tissue sections (7). Despite the durability of this assay, the optical characterization of amyloid has not progressed and is ambiguous (8, 9). The birefringence is rarely quantified, a problem further confounded by the fact that CR does not stain amyloid consistently, and diagnosis by staining depends on the skill of the investigator. Clearly, new opticalcontrast mechanisms are required for simple, reliable amyloid diagnosis (10, 11).Here, we show that recent advances in polarized light microscopy can be used to quickly quantify and refine our description of CR-stained amyloid. In particular, we applied a newly developed imaging system to separate the optical transmission, refractive index anisotropy [linear birefringence (LB)], and optic...

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Section: Resultsmentioning

confidence: 80%

Imaging linear birefringence and dichroism in cerebral amyloid pathologies

Jin

Claborn

Kurimoto

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

187

149

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“…Although Congo red is not a specific marker for IAPP, it is as sensitive a marker for islet amyloid as IAPP immunolabeling (22). In this study, we identified islet amyloid using a Congo red technique (25), the specificity of which was further confirmed in thyroid medullary carcinoma, Alzheimer's disease, and insulinoma (26). Briefly, all 6-m thick pancreatic sections were treated with 1% sodium chloride-hydroxide solution for 20 min and stained with alkaline Congo red solution for another 20 min.…”

Section: Methodsmentioning

confidence: 71%

Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes

et al. 2003

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Islet amyloid has been suggested to be an important link between insulin resistance and ␤-cell dysfunction in type 2 diabetes. To investigate the prevalence and clinicopathological characteristics of islet amyloid, we examined consecutive autopsies of 235 Chinese patients with type 2 diabetes and 533 nondiabetic subjects. Islet amyloid deposits were identified using Congo red staining and quantitated by image analysis. We found that 3.0% of the nondiabetic subjects versus 39.6% of the diabetic patients displayed islet amyloid (P < 0.001). In diabetic patients, the amyloid deposits occupied a mean islet area of 36.2%, which was positively associated with BMI, blood pressure, and glycemic control. Pancreatic fibrosis and fat infiltration were more frequently found in diabetic patients with islet amyloid than those without islet amyloid, whereas pancreatic arteriosclerosis was identified in all diabetic patients. These findings suggest that islet amyloid deposits reflect greater insulin resistance and islet failure in a subgroup of type 2 diabetic patients. Islet failure may also have been exacerbated by fat infiltration, fibrosis, and arteriosclerosis. Optimal blood pressure and metabolic control may reduce these pathological changes and help preserve islet cell mass. Diabetes 52: 2759 -2766, 2003

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“…It has been extensively used to label amyloid deposits in human Alzheimer's disease tissue (Kelenyi, 1967) as well as in transgenic mouse models of amyloid deposition. It is among the stains recommended by the Consortium to Establish a Registry for Alzheimer's Disease for the neuropathological diagnosis of Alzheimer's disease in postmortem tissue (Mirra et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

Growth Arrest of Individual Senile Plaques in a Model of Alzheimer's Disease Observed byIn VivoMultiphoton Microscopy

et al. 2001

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In Alzheimer's disease, amyloid-␤ peptide aggregates in the extracellular space to form senile plaques. The process of plaque deposition and growth has been modeled on the basis of in vitro experiments in ways that lead to divergent predictions: either a diffusion-limited growth model in which plaques grow by first-order kinetics, or a dynamic model of continual deposition and asymmetrical clearance in which plaques reach a stable size and stop growing but evolve morphologically over time. The models have not been tested in vivo because plaques are too small (by several orders of magnitude) for conventional imaging modalities. We now report in vivo multiphoton laser scanning imaging of thioflavine S-stained senile plaques in the Tg2576 transgenic mouse model of Alzheimer's disease to test these biophysical models and show that there is no detectable change in plaque size over extended periods of time. Qualitatively, geometric features remain unchanged over time in the vast majority of the 349 plaques imaged and re-imaged. Intervals as long as 5 months were obtained. Nonetheless, rare examples of growth or shrinkage of individual plaques do occur, and new plaques appear between imaging sessions. These results indicate that thioflavine S-positive plaques appear and then are stable, supporting a dynamic feedback model of plaque growth. Key words: amyloid; transgenic; Alzheimer; two-photon; in vivo imaging; senile plaque; microgliaAggregates of the amyloid-␤ peptide (A␤) form senile plaques, one of the classic neuropathological lesions of Alzheimer's disease. In vitro observations show that A␤ is extremely insoluble and precipitates to form aggregates (Hilbich et al., 1991), and that exogenous A␤ decorates existing plaques and enlarges them according to first-order kinetics (Jarrett and Lansbury, 1993;Esler et al., 1996). These observations led to a model in which a nidus is formed and plaques then grow in a time-and concentrationdependent manner (Jarrett and Lansbury, 1993;Esler et al., 1996).Paradoxically, however, the size distribution of senile plaques appears to remain constant rather than increasing with increasing duration of illness (Hyman et al., 1993). Together with observations on the fine structure of plaques, these data led to a statistical physics-based dynamic feedback model in which a feedback process was postulated to limit plaque growth, leading to stable plaque size and, in principle, the shrinkage of existing plaques (Hyman et al., 1995;Cruz et al., 1997; Urbanc et al., 1999a,b). Distinguishing between these possibilities is important for understanding the life history and pathophysiology of amyloid deposition in Alzheimer's disease, but it has not been possible because direct measurements of plaques in vivo have not been achieved.Tg2576 transgenic mice overexpress a mutant form of the human amyloid precursor protein and develop senile plaques in an age-related fashion, with amyloid-␤ deposits occurring first at ϳ8 -10 months of age (Hsiao et al., 1996;Irizarry et al., 1997).The number of plaques...

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Thioflavin S fluorescent and congo red anisotropic stainings in the histologic demonstration of amyloid

Cited by 101 publications

References 20 publications

Imaging linear birefringence and dichroism in cerebral amyloid pathologies

Imaging linear birefringence and dichroism in cerebral amyloid pathologies

Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes

Growth Arrest of Individual Senile Plaques in a Model of Alzheimer's Disease Observed byIn VivoMultiphoton Microscopy

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