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000270708 1001_ $$00000-0001-7785-482X$$ade Boni, Laura$$b0
000270708 245__ $$aAggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.
000270708 260__ $$aHeidelberg$$bEMBO Press$$c2024
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000270708 520__ $$aSynucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.
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000270708 650_2 $$2MeSH$$aHumans
000270708 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000270708 650_2 $$2MeSH$$aalpha-Synuclein: blood
000270708 650_2 $$2MeSH$$aParkinson Disease: blood
000270708 650_2 $$2MeSH$$aParkinson Disease: metabolism
000270708 650_2 $$2MeSH$$aParkinson Disease: genetics
000270708 650_2 $$2MeSH$$aAged
000270708 650_2 $$2MeSH$$aMale
000270708 650_2 $$2MeSH$$aFemale
000270708 650_2 $$2MeSH$$aMiddle Aged
000270708 650_2 $$2MeSH$$aProtein Multimerization
000270708 650_2 $$2MeSH$$aProtein Aggregates
000270708 650_7 $$2Other$$aParkinson’s disease
000270708 650_7 $$2Other$$aAlpha-synuclein
000270708 650_7 $$2Other$$aBlood
000270708 650_7 $$2Other$$aHuman
000270708 650_7 $$2Other$$aParkinson’s disease
000270708 650_7 $$2Other$$aTetramer
000270708 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000270708 650_7 $$2NLM Chemicals$$aProtein Aggregates
000270708 650_7 $$2NLM Chemicals$$aSNCA protein, human
000270708 7001_ $$aWallis, Amber$$b1
000270708 7001_ $$aHays Watson, Aurelia$$b2
000270708 7001_ $$0P:(DE-2719)2812802$$aRuiz-Riquelme, Alejandro$$b3
000270708 7001_ $$aLeyland, Louise-Ann$$b4
000270708 7001_ $$aBourinaris, Thomas$$b5
000270708 7001_ $$aHannaway, Naomi$$b6
000270708 7001_ $$0P:(DE-2719)2000056$$aWüllner, Ullrich$$b7$$udzne
000270708 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b8$$udzne
000270708 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b9
000270708 7001_ $$0P:(DE-2719)2814178$$aFalkenburger, Björn H$$b10$$udzne
000270708 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b11
000270708 7001_ $$0P:(DE-2719)2811350$$aBähr, Mathias$$b12$$udzne
000270708 7001_ $$0P:(DE-2719)2000058$$aZerr, Inga$$b13$$udzne
000270708 7001_ $$0P:(DE-2719)2811351$$aBürger, Katharina$$b14$$udzne
000270708 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b15
000270708 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b16$$udzne
000270708 7001_ $$0P:(DE-2719)2813524$$aLöhle, Matthias$$b17$$udzne
000270708 7001_ $$0P:(DE-2719)2814194$$aHermann, Wiebke$$b18$$udzne
000270708 7001_ $$0P:(DE-2719)2814326$$aSchott, Björn-Hendrik$$b19
000270708 7001_ $$0P:(DE-2719)2811916$$aBrockmann, Kathrin$$b20$$udzne
000270708 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b21$$udzne
000270708 7001_ $$aHaustein, Katrin$$b22
000270708 7001_ $$0P:(DE-2719)9002874$$aBreuer, Peter$$b23$$udzne
000270708 7001_ $$aHoulden, Henry$$b24
000270708 7001_ $$00000-0002-5092-6325$$aWeil, Rimona S$$b25
000270708 7001_ $$00000-0002-4071-5612$$aBartels, Tim$$b26
000270708 773__ $$0PERI:(DE-600)2485479-7$$a10.1038/s44321-024-00083-5$$gVol. 16, no. 7, p. 1657 - 1674$$n7$$p1657 - 1674$$tEMBO molecular medicine$$v16$$x1757-4676$$y2024
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