Plaque-associated lipids in Alzheimer’s diseased brain tissue visualized by nonlinear microscopy

Kiskis, Juris; Fink, Helen; Nyberg, Lena; Thyr, Jakob; Li, Jia Yi; Enejder, Annika

doi:10.1038/srep13489

Cited by 94 publications

(117 citation statements)

References 57 publications

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“…The pathophysiology of AD is due to a combination of factors including systemic inflammation [3], oxidative stress [4], and beta-amyloid plaque formation [5]. Aging and oxidative stress are associated with declines in hippocampal processing of information [6–8] as demonstrated by the deficits seen in spatial learning, memory formation, and the decline in long term potentiation that is necessary for memory consolidation.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts fromScutellaria baicalensisandAcacia catechu

Yimam

Burnett²,

Brownell

et al. 2016

Behavioural Neurology

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Dementia and cognitive impairment have become the major concerns worldwide due to a significantly aging population, increasing life span and lack of effective pharmacotherapy. In light of limited pharmaceutical drug choices and the socioeconomic implications of these conditions, the search for safe and effective alternatives from natural sources has gained many attractions within the medical food and dietary supplement industry. Two polyphenol extracts derived from roots of Scutellaria baicalensis and heartwoods of Acacia catechu containing free-B-ring flavonoids and flavans, respectively, were combined into a proprietary blend called UP326. A similar bioflavonoid composition, UP446, has been reported with modulation of pathways related to systemic inflammation. To test the effect of UP326 on memory and learning, a radial arm water maze (RAWM) and contextual fear conditioning (CF) were utilized in aged F344 rats fed with UP326 at doses of 3, 7, and 34 mg/kg for 11 weeks. The 7 and 34 mg/kg dosage groups had significantly fewer errors than aged vehicle control animals and their performance was equivalent to young animal controls. In a separate human clinical trial, test subjects orally given 300 mg of UP326 BID for 30 days showed marked improvement in speed and accuracy of processing complex information in computer tasks and reduced their standard deviation of performance compared to baseline and the placebo group. This data suggest that UP326 may help maintain memory, sustain speed of processing, and reduce the number or memory errors as we age.

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Section: Introductionmentioning

confidence: 99%

Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts fromScutellaria baicalensisandAcacia catechu

Yimam

Burnett²,

Brownell

et al. 2016

Behavioural Neurology

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“…As a result, non-destructive identification of amyloids in such tissues becomes possible without introduction of any contaminating agents. This subsequently allows chemical analyses of the identified amyloid structures by vibrational sum-frequency scattering spectroscopy, [70] coherent anti-stokes Raman scattering microscopy, [60,71] and time-of-flight secondary ion mass spectrometry, [72] among other techniques. The fundamental optical properties of amyloids discussed and presented in this paper are essential for continuing efforts with the goal of providing innovative strategies for the study of amyloid fiber structures.…”

Section: Resultsmentioning

confidence: 99%

Label-free imaging of amyloids using their intrinsic linear and nonlinear optical properties

Johansson¹,

Koelsch²

2017

Biomed. Opt. Express

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The optical properties of amyloid fibers are often distinct from those of the source protein in its non-fibrillar form. These differences can be utilized for label-free imaging or characterization of such structures, which is particularly important for understanding amyloid fiber related diseases such as Alzheimer's and Parkinson's disease. We demonstrate that two amyloid forming proteins, insulin and β-lactoglobulin (β-LG), show intrinsic fluorescence with emission spectra that are dependent on the excitation wavelength. Additionally, a new fluorescence peak at about 430 nm emerges for β-LG in its amyloid state. The shift in emission wavelength is related to the red edge excitation shift (REES), whereas the additional fluorescence peak is likely associated with charge delocalization along the fiber backbone. Furthermore, the spherulitic amyloid plaque-like superstructures formed from the respective proteins were imaged label-free with confocal fluorescence, multiphoton excitation fluorescence (MPEF), and second-harmonic generation (SHG) microscopy. The latter two techniques in particular yield images with a high contrast between the amyloid fiber regions and the core of amorphously structured protein. Strong multiphoton absorption (MPA) for the amyloid fibers is a likely contributor to the observed contrast in the MPEF images. The crystalline fibrillar region provides even higher contrast in the SHG images, due to the inherently ordered non-centrosymmetric structure of the fibers together with their non-isotropic arrangement. Finally, we show that MPEF from the insulin spherulites exhibits a spectral dependence on the excitation wavelength. This behavior is consistent with the REES phenomenon, which we hypothesize is the origin of this observation. The presented results suggest that amyloid deposits can be identified and structurally characterized based on their intrinsic optical properties, which is important for probe-less and label-free identification and characterization of amyloid fibers in vitro and in complex biological samples. A. 82(12), 4245-4249 (1985). 8. L. C. Serpell, "Alzheimer's amyloid fibrils: structure and assembly," Biochim. Biophys. Acta 1502(1), 16-30 (2000

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“…There are growing evidences from in vivo and in vitro studies that lipids are incorporated in the amyloid plaques, which can thus be viewed as lipid-protein co-aggregates [[10], [11], [12], [13], [14], [15], [16], [17], [18], [19]]. Numerous studies have reported that lipid membranes can influence the process of protein aggregation [[20], [21], [22]].…”

Section: Introductionmentioning

confidence: 99%

Ganglioside lipids accelerate α-synuclein amyloid formation

Gaspar

Pallbo

Weininger

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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The deposition of α-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of α-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of α-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational change and only weakly catalyse aggregation. Intriguingly, aggregation was also triggered by free ganglioside headgroups, while these caused no conformational change of α-synuclein monomers. Our data reveal that partially folded α-synuclein helical intermediates are not required species in triggering of α-synuclein aggregation.

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Plaque-associated lipids in Alzheimer’s diseased brain tissue visualized by nonlinear microscopy

Cited by 94 publications

References 57 publications

Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts fromScutellaria baicalensisandAcacia catechu

Clinical and Preclinical Cognitive Function Improvement after Oral Treatment of a Botanical Composition Composed of Extracts fromScutellaria baicalensisandAcacia catechu

Label-free imaging of amyloids using their intrinsic linear and nonlinear optical properties

Ganglioside lipids accelerate α-synuclein amyloid formation

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