{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:07:41Z","timestamp":1793502461823,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T00:00:00Z","timestamp":1678492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T00:00:00Z","timestamp":1678492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2145 SyNergy \u2013 ID 390857198"],"award-info":[{"award-number":["EXC 2145 SyNergy \u2013 ID 390857198"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4tsklinik M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer`s disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cross-sectional cohort of 24 transgenic (PS2APP) and 25 wild-type mice (age range: 4.3\u201321.0\u00a0months) underwent 60\u00a0min dynamic [\n                      <jats:sup>18<\/jats:sup>\n                      F]fluorodeprenyl-D2 ([\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED), static 18\u00a0kDa translocator protein (TSPO, [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE-180) and \u03b2-amyloid ([\n                      <jats:sup>18<\/jats:sup>\n                      F]florbetaben) PET imaging. Quantification was performed via image derived input function (IDIF, cardiac input), simplified non-invasive reference tissue modelling (SRTM2, DVR) and late-phase standardized uptake value ratios (SUVr). Immunohistochemical (IHC) analyses of glial fibrillary acidic protein (GFAP) and MAO-B were performed to validate PET imaging by gold standard assessments. Patients belonging to the Alzheimer\u2019s disease continuum (AD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092), Parkinson\u2019s disease (PD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092), multiple system atrophy (MSA,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092), autoimmune encephalitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091), oligodendroglioma (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) and one healthy control underwent 60\u00a0min dynamic [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED PET and the data were analyzed using equivalent quantification strategies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We selected the cerebellum as a pseudo-reference region based on the immunohistochemical comparison of age-matched PS2APP and WT mice. Subsequent PET imaging revealed that PS2APP mice showed elevated hippocampal and thalamic [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED DVR when compared to age-matched WT mice at 5\u00a0months (thalamus:\u2009+\u20094.3%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048), 13\u00a0months (hippocampus:\u2009+\u20097.6%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022) and 19\u00a0months (hippocampus:\u2009+\u200912.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001; thalamus:\u2009+\u200915.2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Specific [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED DVR increases of PS2APP mice occurred earlier when compared to signal alterations in TSPO and \u03b2-amyloid PET and [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED DVR correlated with quantitative immunohistochemistry (hippocampus:\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.720,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; thalamus:\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.727,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Preliminary experience in patients showed [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED V\n                      <jats:sub>T<\/jats:sub>\n                      and SUVr patterns, matching the expected topology of reactive astrogliosis in neurodegenerative (MSA) and neuroinflammatory conditions, whereas the patient with oligodendroglioma and the healthy control indicated [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED binding following the known physiological MAO-B expression in brain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DED PET imaging is a promising approach to assess reactive astrogliosis in AD mouse models and patients with neurological diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-023-02749-2","type":"journal-article","created":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T16:23:13Z","timestamp":1679847793000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["[18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data"],"prefix":"10.1186","volume":"20","author":[{"given":"Anna","family":"Ballweg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Klaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Vogler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Katzdobler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Wind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Zatcepin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle I.","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birkan","family":"Secgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Eckenweber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Bohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bernhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urban","family":"Fietzek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris-Stephan","family":"Rauchmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Stoecklein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Quach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Scheifele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Simmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Koglin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Stephens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bartenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg C.","family":"Tonn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie L.","family":"Albert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"K\u00fcmpfel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kerschensteiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Perneczky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Paeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,11]]},"reference":[{"key":"2749_CR1","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, David E, Baruch K, Lara-Astaiso D, Toth B, et al. A unique microglia type associated with restricting development of Alzheimer\u2019s disease. Cell. 2017;169:1276-1290.e1217.","journal-title":"Cell"},{"key":"2749_CR2","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Munch AE, Chung WS, Peterson TC, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541:481\u20137.","journal-title":"Nature"},{"key":"2749_CR3","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12974-021-02158-3","volume":"18","author":"J Rostami","year":"2021","unstructured":"Rostami J, Mothes T, Kolahdouzan M, Eriksson O, Moslem M, Bergstr\u00f6m J, Ingelsson M, O\u2019Callaghan P, Healy LM, Falk A, Erlandsson A. Crosstalk between astrocytes and microglia results in increased degradation of \u03b1-synuclein and amyloid-\u03b2 aggregates. J Neuroinflammation. 2021;18:124.","journal-title":"J Neuroinflammation"},{"key":"2749_CR4","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/S0140-6736(10)61349-9","volume":"377","author":"C Ballard","year":"2011","unstructured":"Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. Alzheimer\u2019s disease. Lancet. 2011;377:1019\u201331.","journal-title":"Lancet"},{"key":"2749_CR5","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, et al. NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 2018;14:535\u201362.","journal-title":"Alzheimers Dement"},{"key":"2749_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3389\/fnmol.2017.00427","volume":"10","author":"RE Gonz\u00e1lez-Reyes","year":"2017","unstructured":"Gonz\u00e1lez-Reyes RE, Nava-Mesa MO, Vargas-S\u00e1nchez K, Ariza-Salamanca D, Mora-Mu\u00f1oz L. Involvement of astrocytes in Alzheimer\u2019s disease from a neuroinflammatory and oxidative stress perspective. Front Mol Neurosci. 2017;10:427.","journal-title":"Front Mol Neurosci"},{"key":"2749_CR7","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s00259-015-3047-0","volume":"42","author":"E Rodriguez-Vieitez","year":"2015","unstructured":"Rodriguez-Vieitez E, Ni R, Guly\u00e1s B, T\u00f3th M, H\u00e4ggkvist J, Halldin C, Voytenko L, Marutle A, Nordberg A. Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study. Eur J Nucl Med Mol Imaging. 2015;42:1119\u201332.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2749_CR8","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1093\/brain\/awv404","volume":"139","author":"E Rodriguez-Vieitez","year":"2016","unstructured":"Rodriguez-Vieitez E, Saint-Aubert L, Carter SF, Almkvist O, Farid K, Sch\u00f6ll M, Chiotis K, Thordardottir S, Graff C, Wall A, et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer\u2019s disease. Brain. 2016;139:922\u201336.","journal-title":"Brain"},{"key":"2749_CR9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012109","author":"B Bellaver","year":"2021","unstructured":"Bellaver B, Ferrari-Souza JP, da Uglione Ros L, Carter SF, Rodriguez-Vieitez E, Nordberg A, Pellerin L, Rosa-Neto P, Leffa DT, Zimmer ER. Astrocyte biomarkers in Alzheimer disease: a systematic review and meta-analysis. Neurology. 2021. https:\/\/doi.org\/10.1212\/WNL.0000000000012109.","journal-title":"Neurology"},{"key":"2749_CR10","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","volume":"24","author":"C Escartin","year":"2021","unstructured":"Escartin C, Galea E, Lakatos A, O\u2019Callaghan JP, Petzold GC, Serrano-Pozo A, Steinh\u00e4user C, Volterra A, Carmignoto G, Agarwal A, et al. Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci. 2021;24:312\u201325.","journal-title":"Nat Neurosci"},{"key":"2749_CR11","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1023\/A:1007677003387","volume":"25","author":"LF Eng","year":"2000","unstructured":"Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969\u20132000). Neurochem Res. 2000;25:1439\u201351.","journal-title":"Neurochem Res"},{"key":"2749_CR12","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","volume":"32","author":"MV Sofroniew","year":"2009","unstructured":"Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009;32:638\u201347.","journal-title":"Trends Neurosci"},{"key":"2749_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.807435","volume":"16","author":"R Harada","year":"2022","unstructured":"Harada R, Furumoto S, Kudo Y, Yanai K, Villemagne VL, Okamura N. Imaging of reactive astrogliosis by positron emission tomography. Front Neurosci. 2022;16: 807435.","journal-title":"Front Neurosci"},{"key":"2749_CR14","doi-asserted-by":"publisher","first-page":"6385","DOI":"10.1073\/pnas.79.20.6385","volume":"79","author":"P Levitt","year":"1982","unstructured":"Levitt P, Pintar JE, Breakefield XO. Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci USA. 1982;79:6385\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2749_CR15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2967\/jnumed.110.087031","volume":"53","author":"SF Carter","year":"2012","unstructured":"Carter SF, Scholl M, Almkvist O, Wall A, Engler H, Langstrom B, Nordberg A. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012;53:37\u201346.","journal-title":"J Nucl Med"},{"key":"2749_CR16","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2967\/jnumed.115.161083","volume":"57","author":"S Nag","year":"2016","unstructured":"Nag S, Fazio P, Lehmann L, Kettschau G, Heinrich T, Thiele A, Svedberg M, Amini N, Leesch S, Catafu AM, et al. In vivo and in vitro characterization of a novel MAO-B inhibitor radioligand, 18F-labeled deuterated fluorodeprenyl. J Nucl Med. 2016;57:315\u201320.","journal-title":"J Nucl Med"},{"key":"2749_CR17","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263254","author":"VL Villemagne","year":"2022","unstructured":"Villemagne VL, Harada R, Dore V, Furumoto S, Mulligan R, Kudo Y, Burnham S, Krishnadas N, Bozinovski S, Huang K, et al. First-in-human evaluation of (18)F-SMBT-1, a novel (18)F-labeled MAO-B PET tracer for imaging reactive astrogliosis. J Nucl Med. 2022. https:\/\/doi.org\/10.2967\/jnumed.121.263254.","journal-title":"J Nucl Med"},{"key":"2749_CR18","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263255","author":"VL Villemagne","year":"2022","unstructured":"Villemagne VL, Harada R, Dore V, Furumoto S, Mulligan R, Kudo Y, Burnham S, Krishnadas N, Bourgeat P, Xia Y, et al. Assessing reactive astrogliosis with (18)F-SMBT-1 across the Alzheimer\u2019s disease spectrum. J Nucl Med. 2022. https:\/\/doi.org\/10.2967\/jnumed.121.263255.","journal-title":"J Nucl Med"},{"key":"2749_CR19","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.2967\/jnumed.120.242750","volume":"61","author":"C Sacher","year":"2020","unstructured":"Sacher C, Blume T, Beyer L, Biechele G, Sauerbeck J, Eckenweber F, Deussing M, Focke C, Parhizkar S, Lindner S, et al. Asymmetry of fibrillar plaque burden in amyloid mouse models. J Nucl Med. 2020;61:1825\u201331.","journal-title":"J Nucl Med"},{"key":"2749_CR20","doi-asserted-by":"publisher","first-page":"8989","DOI":"10.1523\/JNEUROSCI.23-26-08989.2003","volume":"23","author":"JG Richards","year":"2003","unstructured":"Richards JG, Higgins GA, Ouagazzal AM, Ozmen L, Kew JN, Bohrmann B, Malherbe P, Brockhaus M, Loetscher H, Czech C, et al. PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation. J Neurosci. 2003;23:8989\u20139003.","journal-title":"J Neurosci"},{"key":"2749_CR21","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1159\/000170884","volume":"6","author":"L Ozmen","year":"2009","unstructured":"Ozmen L, Albientz A, Czech C, Jacobsen H. Expression of transgenic APP mRNA is the key determinant for beta-amyloid deposition in PS2APP transgenic mice. Neurodegener Dis. 2009;6:29\u201336.","journal-title":"Neurodegener Dis"},{"key":"2749_CR22","doi-asserted-by":"publisher","first-page":"8964","DOI":"10.7150\/thno.64022","volume":"11","author":"G Biechele","year":"2021","unstructured":"Biechele G, Blume T, Deussing M, Zott B, Shi Y, Xiang X, Franzmeier N, Kleinberger G, Peters F, Ochs K, et al. Pre-therapeutic microglia activation and sex determine therapy effects of chronic immunomodulation. Theranostics. 2021;11:8964\u201376.","journal-title":"Theranostics"},{"key":"2749_CR23","doi-asserted-by":"publisher","first-page":"954","DOI":"10.2967\/jnumed.115.167858","volume":"57","author":"M Brendel","year":"2016","unstructured":"Brendel M, Probst F, Jaworska A, Overhoff F, Korzhova V, Albert NL, Beck R, Lindner S, Gildehaus FJ, Baumann K, et al. Glial activation and glucose metabolism in a transgenic amyloid mouse model: a triple-tracer PET study. J Nucl Med. 2016;57:954\u201360.","journal-title":"J Nucl Med"},{"key":"2749_CR24","doi-asserted-by":"publisher","first-page":"117","DOI":"10.2967\/jnumed.120.261858","volume":"63","author":"G Biechele","year":"2022","unstructured":"Biechele G, Monasor LS, Wind K, Blume T, Parhizkar S, Arzberger T, Sacher C, Beyer L, Eckenweber F, Gildehaus FJ, et al. Glitter in the darkness? Nonfibrillar beta-amyloid plaque components significantly impact the beta-amyloid PET signal in mouse models of alzheimer disease. J Nucl Med. 2022;63:117\u201324.","journal-title":"J Nucl Med"},{"key":"2749_CR25","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1186\/s12974-020-02046-2","volume":"17","author":"G Biechele","year":"2020","unstructured":"Biechele G, Franzmeier N, Blume T, Ewers M, Luque JM, Eckenweber F, Sacher C, Beyer L, Ruch-Rubinstein F, Lindner S, et al. Glial activation is moderated by sex in response to amyloidosis but not to tau pathology in mouse models of neurodegenerative diseases. J Neuroinflammation. 2020;17:374.","journal-title":"J Neuroinflammation"},{"key":"2749_CR26","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.2967\/jnumed.119.227322","volume":"60","author":"C Sacher","year":"2019","unstructured":"Sacher C, Blume T, Beyer L, Peters F, Eckenweber F, Sgobio C, Deussing M, Albert NL, Unterrainer M, Lindner S, et al. Longitudinal PET monitoring of amyloidosis and microglial activation in a second-generation amyloid-beta mouse model. J Nucl Med. 2019;60:1787\u201393.","journal-title":"J Nucl Med"},{"key":"2749_CR27","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3389\/fnins.2016.00045","volume":"10","author":"F Overhoff","year":"2016","unstructured":"Overhoff F, Brendel M, Jaworska A, Korzhova V, Delker A, Probst F, Focke C, Gildehaus FJ, Carlsen J, Baumann K, et al. Automated spatial brain normalization and hindbrain white matter reference tissue give improved [(18)F]-Florbetaben PET quantitation in Alzheimer\u2019s model mice. Front Neurosci. 2016;10:45.","journal-title":"Front Neurosci"},{"key":"2749_CR28","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.neuroscience.2005.07.014","volume":"135","author":"Y Ma","year":"2005","unstructured":"Ma Y, Hof PR, Grant SC, Blackband SJ, Bennett R, Slatest L, McGuigan MD, Benveniste H. A three-dimensional digital atlas database of the adult C57BL\/6J mouse brain by magnetic resonance microscopy. Neuroscience. 2005;135:1203\u201315.","journal-title":"Neuroscience"},{"key":"2749_CR29","doi-asserted-by":"publisher","first-page":"eabe5640","DOI":"10.1126\/scitranslmed.abe5640","volume":"13","author":"X Xiang","year":"2021","unstructured":"Xiang X, Wind K, Wiedemann T, Blume T, Shi Y, Briel N, Beyer L, Biechele G, Eckenweber F, Zatcepin A, et al. Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases. Sci Transl Med. 2021;13:eabe5640.","journal-title":"Sci Transl Med."},{"key":"2749_CR30","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/jcbfm.1990.127","volume":"10","author":"J Logan","year":"1990","unstructured":"Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, MacGregor RR, Hitzemann R, Bendriem B, Gatley SJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab. 1990;10:740\u20137.","journal-title":"J Cereb Blood Flow Metab"},{"key":"2749_CR31","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.2967\/jnumed.112.114660","volume":"54","author":"A Rominger","year":"2013","unstructured":"Rominger A, Brendel M, Burgold S, Keppler K, Baumann K, Xiong G, Mille E, Gildehaus FJ, Carlsen J, Schlichtiger J, et al. Longitudinal assessment of cerebral beta-amyloid deposition in mice overexpressing Swedish mutant beta-amyloid precursor protein using 18F-florbetaben PET. J Nucl Med. 2013;54:1127\u201334.","journal-title":"J Nucl Med"},{"key":"2749_CR32","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1001\/jamaneurol.2020.2526","volume":"77","author":"M Brendel","year":"2020","unstructured":"Brendel M, Barthel H, van Eimeren T, Marek K, Beyer L, Song M, Palleis C, Gehmeyr M, Fietzek U, Respondek G, et al. Assessment of 18F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol. 2020;77:1408\u201319.","journal-title":"JAMA Neurol"},{"key":"2749_CR33","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1126\/science.3099392","volume":"235","author":"JS Fowler","year":"1987","unstructured":"Fowler JS, MacGregor RR, Wolf AP, Arnett CD, Dewey SL, Schlyer D, Christman D, Logan J, Smith M, Sachs H, et al. Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. Science. 1987;235:481\u20135.","journal-title":"Science"},{"key":"2749_CR34","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/jcbfm.2014.34","volume":"34","author":"PM Rusjan","year":"2014","unstructured":"Rusjan PM, Wilson AA, Miler L, Fan I, Mizrahi R, Houle S, Vasdev N, Meyer JH. Kinetic modeling of the monoamine oxidase B radioligand [(1)(1)C]SL25.1188 in human brain with high-resolution positron emission tomography. J Cereb Blood Flow Metab. 2014;34:883\u20139.","journal-title":"J Cereb Blood Flow Metab."},{"key":"2749_CR35","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1007\/s00259-011-1895-9","volume":"38","author":"AF Santillo","year":"2011","unstructured":"Santillo AF, Gambini JP, Lannfelt L, L\u00e5ngstr\u00f6m B, Ulla-Marja L, Kilander L, Engler H. In vivo imaging of astrocytosis in Alzheimer\u2019s disease: an 11C-L-deuteriodeprenyl and PIB PET study. Eur J Nucl Med Mol Imaging. 2011;38:2202\u20138.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2749_CR36","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s11307-017-1153-z","volume":"20","author":"M Olsen","year":"2018","unstructured":"Olsen M, Aguilar X, Sehlin D, Fang XT, Antoni G, Erlandsson A, Syv\u00e4nen S. Astroglial responses to amyloid-beta progression in a mouse model of Alzheimer\u2019s disease. Mol Imaging Biol. 2018;20:605\u201314.","journal-title":"Mol Imaging Biol"},{"key":"2749_CR37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.molmed.2018.11.006","volume":"25","author":"SF Carter","year":"2019","unstructured":"Carter SF, Herholz K, Rosa-Neto P, Pellerin L, Nordberg A, Zimmer ER. Astrocyte biomarkers in Alzheimer\u2019s disease. Trends Mol Med. 2019;25:77\u201395.","journal-title":"Trends Mol Med"},{"key":"2749_CR38","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.jalz.2019.09.004","volume":"16","author":"FM Elahi","year":"2020","unstructured":"Elahi FM, Casaletto KB, La Joie R, Walters SM, Harvey D, Wolf A, Edwards L, Rivera-Contreras W, Karydas A, Cobigo Y, et al. Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer\u2019s disease. Alzheimers Dement. 2020;16:681\u201395.","journal-title":"Alzheimers Dement"},{"key":"2749_CR39","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41398-020-01137-1","volume":"11","author":"P Chatterjee","year":"2021","unstructured":"Chatterjee P, Pedrini S, Stoops E, Goozee K, Villemagne VL, Asih PR, Verberk IMW, Dave P, Taddei K, Sohrabi HR, et al. Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer\u2019s disease. Transl Psychiatry. 2021;11:27.","journal-title":"Transl Psychiatry"},{"key":"2749_CR40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neuint.2010.10.013","volume":"58","author":"B Guly\u00e1s","year":"2011","unstructured":"Guly\u00e1s B, Pavlova E, K\u00e1sa P, Gulya K, Bakota L, V\u00e1rszegi S, Keller E, Horv\u00e1th MC, Nag S, Hermecz I, et al. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography. Neurochem Int. 2011;58:60\u20138.","journal-title":"Neurochem Int"},{"key":"2749_CR41","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3389\/fnagi.2019.00249","volume":"11","author":"S Schonecker","year":"2019","unstructured":"Schonecker S, Brendel M, Palleis C, Beyer L, Hoglinger GU, Schuh E, Rauchmann BS, Sauerbeck J, Rohrer G, Sonnenfeld S, et al. PET imaging of astrogliosis and tau facilitates diagnosis of Parkinsonian syndromes. Front Aging Neurosci. 2019;11:249.","journal-title":"Front Aging Neurosci"},{"key":"2749_CR42","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1093\/brain\/awz260","volume":"142","author":"H Wilson","year":"2019","unstructured":"Wilson H, Dervenoulas G, Pagano G, Tyacke RJ, Polychronis S, Myers J, Gunn RN, Rabiner EA, Nutt D, Politis M. Imidazoline 2 binding sites reflecting astroglia pathology in Parkinson\u2019s disease: an in vivo11C-BU99008 PET study. Brain. 2019;142:3116\u201328.","journal-title":"Brain"},{"key":"2749_CR43","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1093\/brain\/awx172","volume":"140","author":"J Tong","year":"2017","unstructured":"Tong J, Rathitharan G, Meyer JH, Furukawa Y, Ang LC, Boileau I, Guttman M, Hornykiewicz O, Kish SJ. Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency disorders. Brain. 2017;140:2460\u201374.","journal-title":"Brain"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-023-02749-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-023-02749-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-023-02749-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T16:23:47Z","timestamp":1679847827000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-023-02749-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,11]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["2749"],"URL":"https:\/\/doi.org\/10.1186\/s12974-023-02749-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2247888\/v1","asserted-by":"object"}]},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,11]]},"assertion":[{"value":"7 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the local ethics committee of the medical faculty of the LMU Munich (Application Number: 21-0721) and written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"NK, AM and AWS are employees of Life Molecular Imaging. MB received research funding from Life Molecular Imaging. No other potential competing interest relevant to this article exist.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}