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Increased CSF-decor...
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Jiang, R. C.Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, S-17164 Stockholm, Sweden.;First Hosp Jilin Univ, Dept Otolaryngol Head & Neck Surg, Changchun 130021, Peoples R China.
(author)
Increased CSF-decorin predicts brain pathological changes driven by Alzheimer's A beta amyloidosis
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-07-04
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Springer Science and Business Media LLC,2022
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/319036
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https://gup.ub.gu.se/publication/319036URI
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https://doi.org/10.1186/s40478-022-01398-5DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-481185URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-187434URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:150142216URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding Agencies|Karolinska Institute; Hallsten Research Foundation; Swedish Research Council; Swedish Brain foundation; Torsten Soderberg Foundation; Erling-Persson Family Foundation; China Scholarship Council; Swedish Research Council [2015-4870]; uropean Unions Horizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant [676144]; Gun and Bertil Stohnes Foundation; Gamla Tjanarinnor grant; Margaretha af Ugglas Stiftelse; Alzheimerfonden [AF-930934]; Alzheimerfonden; Hjarnfonden; Swedish Brain Foundation [ALZ2022-0004, FO-2020-0207]; European Research Council [681712]; Swedish State Support for Clinical Research [ALFGBG-720931]; Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862]; AD Strategic Fund; Alzheimers Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]; Olav Thon Foundation; Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden [FO2019-0228]; European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [860197]; European Union Joint Program for Neurodegenerative Disorders [JPND2021-00694]; UK Dementia Research Institute at UCL
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Cerebrospinal fluid (CSF) biomarkers play an important role in diagnosing Alzheimer's disease (AD) which is characterized by amyloid-beta (A beta) amyloidosis. Here, we used two App knock-in mouse models, App(NL-F/NL-F) and App(NL-G-F/NL-G-F), exhibiting AD-like A beta pathology to analyze how the brain pathologies translate to CSF proteomes by label-free mass spectrometry (MS). This identified several extracellular matrix (ECM) proteins as significantly altered in App knock-in mice. Next, we compared mouse CSF proteomes with previously reported human CSF MS results acquired from patients across the AD spectrum. Intriguingly, the ECM protein decorin was similarly and significantly increased in both App(NL-F/NL-F) and App(NL-G-F/NL-G-F) mice, strikingly already at three months of age in the App(NL-F/NL-F) mice and preclinical AD subjects having abnormal CSF-A beta 42 but normal cognition. Notably, in this group of subjects, CSF-decorin levels positively correlated with CSF-A beta 42 levels indicating that the change in CSF-decorin is associated with early A beta amyloidosis. Importantly, receiver operating characteristic analysis revealed that CSF-decorin can predict a specific AD subtype having innate immune activation and potential choroid plexus dysfunction in the brain. Consistently, in App(NL-F/NL-F) mice, increased CSF-decorin correlated with both AP plaque load and with decorin levels in choroid plexus. In addition, a low concentration of human A beta 42 induces decorin secretion from mouse primary neurons. Interestingly, we finally identify decorin to activate neuronal autophagy through enhancing lysosomal function. Altogether, the increased CSF-decorin levels occurring at an early stage of A beta amyloidosis in the brain may reflect pathological changes in choroid plexus, present in a subtype of AD subjects.
Subject headings and genre
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Smailovic, U.Karolinska Institutet
(author)
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Haytural, H.Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, S-17164 Stockholm, Sweden.
(author)
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Tijms, B. M.Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam UMC,Amsterdam Neurosci, NL-1007 MB Amsterdam, Netherlands.
(author)
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Li, H.Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, S-17164 Stockholm, Sweden.;Shaanxi Chinese Med Univ, Affiliated Hosp 2, Dept Neurosurg, Xianyang 712000, Shaanxi, Peoples R China.
(author)
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Haret, R. M.Carol Davila Univ Med & Pharm, Div Physiol & Neurosci, Bucharest 050474, Romania.
(author)
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Shevchenko, GannaUppsala universitet,Analytisk kemi,Uppsala Univ, Sweden(Swepub:uu)gansc354
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Chen, G. F.Karolinska Institutet
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Abelein, A.Karolinska Institutet
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Gobom, JohanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41345 Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, S-41345 Mölndal, Sweden.(Swepub:gu)xgobjo
(author)
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Frykman, S.Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, S-17164 Stockholm, Sweden.
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Sekiguchi, M.RIKEN Ctr Brain Sci, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan.
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Fujioka, R.RIKEN Ctr Brain Sci, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan.
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Watamura, N.RIKEN Ctr Brain Sci, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan.
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Sasaguri, H.RIKEN Ctr Brain Sci, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan.
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Nyström, SofieLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)sofny42
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Hammarström, PerLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)perha81
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Saido, T. C.RIKEN Ctr Brain Sci, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan.
(author)
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Jelic, V.Karolinska Institutet
(author)
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Syvänen, StinaUppsala universitet,Geriatrik,Uppsala Univ, Sweden(Swepub:uu)stsyv838
(author)
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41345 Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, S-41345 Mölndal, Sweden.;UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England.;UCL, UK Dementia Res Inst, London WC1E 6BT, England.;Hong Kong Ctr Neurodegenerat Dis, Hong Kong, Peoples R China.(Swepub:gu)xzethe
(author)
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Winblad, B.Karolinska Institutet
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Bergquist, JonasUppsala universitet,Analytisk kemi,Uppsala Univ, Sweden(Swepub:uu)jbe25356
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Visser, P. J.
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Nilsson, P.Karolinska Institutet
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Karolinska InstitutetKarolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, S-17164 Stockholm, Sweden.;First Hosp Jilin Univ, Dept Otolaryngol Head & Neck Surg, Changchun 130021, Peoples R China.
(creator_code:org_t)
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In:Acta Neuropathologica Communications: Springer Science and Business Media LLC10:12051-5960
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Jiang, R. C.
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Smailovic, U.
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Haytural, H.
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Tijms, B. M.
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Li, H.
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Haret, R. M.
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Shevchenko, Gann ...
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Chen, G. F.
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Abelein, A.
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Gobom, Johan
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Frykman, S.
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Sekiguchi, M.
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Fujioka, R.
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Watamura, N.
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Sasaguri, H.
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Nyström, Sofie
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Hammarström, Per
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Saido, T. C.
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Jelic, V.
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Syvänen, Stina
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Zetterberg, Henr ...
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Winblad, B.
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Bergquist, Jonas
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Visser, P. J.
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Nilsson, P.
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