000259712 001__ 259712 000259712 005__ 20231004134657.0 000259712 0247_ $$2doi$$a10.1016/j.nbas.2023.100086 000259712 0247_ $$2pmid$$apmid:37559953 000259712 0247_ $$2pmc$$apmc:PMC10407822 000259712 0247_ $$2altmetric$$aaltmetric:153155965 000259712 037__ $$aDZNE-2023-00784 000259712 041__ $$aEnglish 000259712 082__ $$a610 000259712 1001_ $$aEkmark-Lewén, S.$$b0 000259712 245__ $$aReduction of brain stem pathology and transient amelioration of early cognitive symptoms in transgenic mice treated with a monoclonal antibody against α-synuclein oligomers/protofibrils. 000259712 260__ $$aAmsterdam$$bElsevier$$c2023 000259712 3367_ $$2DRIVER$$aarticle 000259712 3367_ $$2DataCite$$aOutput Types/Journal article 000259712 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1692959108_28574 000259712 3367_ $$2BibTeX$$aARTICLE 000259712 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000259712 3367_ $$00$$2EndNote$$aJournal Article 000259712 520__ $$aImmunotherapy against alpha-synuclein (α-syn) is a promising novel treatment strategy for Parkinson's disease (PD) and related α-synucleinopathies. We have previously shown that systemic treatment with the monoclonal oligomer/protofibril-selective antibody mAb47 targeting cytotoxic α-syn leads to reduced central nervous system levels of such species as well as an indication of reduced late-stage symptoms in aged (Thy-1)-h[A30P] α-syn transgenic mice. Here, we performed an early-onset long-term treatment study with this antibody to evaluate effects on brain pathology and behavioral outcomes in the same mouse model. Compared to the placebo group, the treatment strongly reduced phosphorylated α-syn (pS129 α-syn) pathology in the upper brain stem. Moreover, a preserved recognition memory and risk assessment behavior could be seen in antibody-treated mice at six months of age, even although these effects were no longer significant at eleven months of age. Importantly, no evidence of inflammatory responses or other potential toxic effects was seen with the treatment. Taken together, this study supports the strategy to target α-syn oligomers/protofibrils with monoclonal antibodies to counteract early symptoms and slow down the progression of PD and other α-synucleinopathies. 000259712 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000259712 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000259712 650_7 $$2Other$$aAlpha-synuclein transgenic mice 000259712 650_7 $$2Other$$aBehavioral outcome 000259712 650_7 $$2Other$$aImmunotherapy 000259712 650_7 $$2Other$$aOligomer/protofibril-selective antibody 000259712 650_7 $$2Other$$aOligomers 000259712 7001_ $$aAniszewska, A.$$b1 000259712 7001_ $$aMolisak, A.$$b2 000259712 7001_ $$aGumucio, A.$$b3 000259712 7001_ $$aLindström, V.$$b4 000259712 7001_ $$0P:(DE-2719)2810803$$aKahle, P. J.$$b5$$udzne 000259712 7001_ $$aNordström, E.$$b6 000259712 7001_ $$aMöller, C.$$b7 000259712 7001_ $$aFälting, J.$$b8 000259712 7001_ $$aLannfelt, L.$$b9 000259712 7001_ $$aBergström, J.$$b10 000259712 7001_ $$aIngelsson, M.$$b11 000259712 773__ $$0PERI:(DE-600)3062875-1$$a10.1016/j.nbas.2023.100086$$gVol. 4, p. 100086 -$$p100086$$tAging brain$$v4$$x2589-9589$$y2023 000259712 8564_ $$uhttps://pub.dzne.de/record/259712/files/DZNE-2023-00784.pdf$$yOpenAccess 000259712 8564_ $$uhttps://pub.dzne.de/record/259712/files/DZNE-2023-00784.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000259712 909CO $$ooai:pub.dzne.de:259712$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000259712 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810803$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE 000259712 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0 000259712 9141_ $$y2023 000259712 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 000259712 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000259712 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2022-11-23 000259712 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2022-11-23 000259712 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-23 000259712 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-23 000259712 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-05-09T12:01:05Z 000259712 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-05-09T12:01:05Z 000259712 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-05-09T12:01:05Z 000259712 9201_ $$0I:(DE-2719)1210000-4$$kAG Kahle$$lFunctional Neurogenetics$$x0 000259712 980__ $$ajournal 000259712 980__ $$aVDB 000259712 980__ $$aUNRESTRICTED 000259712 980__ $$aI:(DE-2719)1210000-4 000259712 9801_ $$aFullTexts