{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:55:07Z","timestamp":1791464107340,"version":"4.3.4"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG062421"],"award-info":[{"award-number":["P30AG062421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K08AG064069"],"award-info":[{"award-number":["K08AG064069"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013721","name":"Real Colegio Complutense at Harvard University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013721","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Prince Mahidol Award Youth Program"},{"name":"Martin L. and Sylvia Seevak Hoffman Fellowship for Alzheimer's Research"},{"DOI":"10.13039\/100020334","name":"Karen Toffler Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020334","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Harrison Gardner Jr. Innovation Award"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reactive astrogliosis accompanies the two neuropathological hallmarks of Alzheimer\u2019s disease (AD)\u2014A\u03b2 plaques and neurofibrillary tangles\u2014and parallels neurodegeneration in AD and AD-related dementias (ADRD). Thus, there is growing interest in developing imaging and fluid biomarkers of reactive astrogliosis for AD\/ADRD diagnosis and prognostication. Monoamine oxidase-B (MAO-B) is emerging as a target for PET imaging radiotracers of reactive astrogliosis. However, a thorough characterization of MAO-B expression in postmortem control and AD\/ADRD brains is lacking. We sought to: (1) identify the primary cell type(s) expressing MAO-B in control and AD brains; (2) quantify MAO-B immunoreactivity in multiple brain regions of control and AD donors as a proxy for PET radiotracer uptake; (3) correlate MAO-B level with local AD neuropathological changes, reactive glia, and cortical atrophy; (4) determine whether the <jats:italic>MAOB<\/jats:italic> rs1799836 SNP genotype impacts MAO-B expression level; (5) compare MAO-B immunoreactivity across AD\/ADRD, including Lewy body diseases (LBD) and frontotemporal lobar degenerations with tau (FTLD-Tau) and TDP-43 (FTLD-TDP). We found that MAO-B is mainly expressed by subpial and perivascular cortical astrocytes as well as by fibrous white matter astrocytes in control brains, whereas in AD brains, MAO-B is significantly upregulated by both cortical reactive astrocytes and white matter astrocytes across temporal, frontal, and occipital lobes. By contrast, MAO-B expression level was unchanged and lowest in cerebellum. Cortical MAO-B expression was independently associated with cortical atrophy and local measures of reactive astrocytes and microglia, and significantly increased in reactive astrocytes surrounding Thioflavin-S+ dense-core A\u03b2 plaques. MAO-B expression was not affected by the <jats:italic>MAOB<\/jats:italic> rs1799836 SNP genotype. MAO-B expression was also significantly increased in the frontal cortex and white matter of donors with corticobasal degeneration, Pick\u2019s disease, and FTLD-TDP, but not in LBD or progressive supranuclear palsy. These findings support ongoing efforts to develop MAO-B-based PET radiotracers to image reactive astrogliosis in AD\/ADRD.<\/jats:p>","DOI":"10.1007\/s00401-024-02712-2","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T14:03:07Z","timestamp":1712152987000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Characterization of monoamine oxidase-B (MAO-B) as a biomarker of reactive astrogliosis in Alzheimer\u2019s disease and related dementias"],"prefix":"10.1007","volume":"147","author":[{"given":"Methasit","family":"Jaisa-aad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Mu\u00f1oz-Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly A.","family":"Healey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0899-7530","authenticated-orcid":false,"given":"Alberto","family":"Serrano-Pozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"2712_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40478-019-0686-6","volume":"7","author":"C Aguero","year":"2019","unstructured":"Aguero C, Dhaynaut M, Normandin MD, Amaral AC, Guehl NJ, Neelamegam R et al (2019) Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta Neuropathol Commun 7:37. https:\/\/doi.org\/10.1186\/s40478-019-0686-6","journal-title":"Acta Neuropathol Commun"},{"key":"2712_CR2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00401-020-02255-2","volume":"141","author":"J Attems","year":"2021","unstructured":"Attems J, Toledo JB, Walker L, Gelpi E, Gentleman S, Halliday G et al (2021) Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study. Acta Neuropathol (Berl) 141:159\u2013172. https:\/\/doi.org\/10.1007\/s00401-020-02255-2","journal-title":"Acta Neuropathol (Berl)"},{"key":"2712_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00439-001-0652-8","volume":"110","author":"J Balciuniene","year":"2002","unstructured":"Balciuniene J, Emilsson L, Oreland L, Pettersson U, Jazin E (2002) Investigation of the functional effect of monoamine oxidase polymorphisms in human brain. Hum Genet 110:1\u20137. https:\/\/doi.org\/10.1007\/s00439-001-0652-8","journal-title":"Hum Genet"},{"key":"2712_CR4","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12974-023-02749-2","volume":"20","author":"A Ballweg","year":"2023","unstructured":"Ballweg A, Klaus C, Vogler L, Katzdobler S, Wind K, Zatcepin A et al (2023) [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data. J Neuroinflammation 20:68. https:\/\/doi.org\/10.1186\/s12974-023-02749-2","journal-title":"J Neuroinflammation"},{"key":"2712_CR5","doi-asserted-by":"publisher","first-page":"e2944","DOI":"10.1212\/WNL.0000000000012109","volume":"96","author":"B Bellaver","year":"2021","unstructured":"Bellaver B, Ferrari-Souza JP, Uglione Da Ros L, Carter SF, Rodriguez-Vieitez E, Nordberg A et al (2021) Astrocyte biomarkers in Alzheimer disease: a systematic review and meta-analysis. Neurology 96:e2944\u2013e2955. https:\/\/doi.org\/10.1212\/WNL.0000000000012109","journal-title":"Neurology"},{"key":"2712_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000442","author":"J Birks","year":"2003","unstructured":"Birks J, Flicker L (2003) Selegiline for Alzheimer\u2019s disease. Cochrane Datab Syst Rev. https:\/\/doi.org\/10.1002\/14651858.CD000442","journal-title":"Cochrane Datab Syst Rev"},{"key":"2712_CR7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00401-010-0705-y","volume":"120","author":"D Boche","year":"2010","unstructured":"Boche D, Donald J, Love S, Harris S, Neal JW, Holmes C et al (2010) Reduction of aggregated Tau in neuronal processes but not in the cell bodies after abeta42 immunisation in Alzheimer\u2019s disease. Acta Neuropathol (Berl) 120:13\u201320. https:\/\/doi.org\/10.1007\/s00401-010-0705-y","journal-title":"Acta Neuropathol (Berl)"},{"key":"2712_CR8","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00401-007-0237-2","volume":"114","author":"NJ Cairns","year":"2007","unstructured":"Cairns NJ, Bigio EH, Mackenzie IRA, Neumann M, Lee VM-Y, Hatanpaa KJ et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol (Berl) 114:5\u201322. https:\/\/doi.org\/10.1007\/s00401-007-0237-2","journal-title":"Acta Neuropathol (Berl)"},{"key":"2712_CR9","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 (2019) Astrocyte biomarkers in Alzheimer\u2019s Disease. Trends Mol Med 25:77\u201395. https:\/\/doi.org\/10.1016\/j.molmed.2018.11.006","journal-title":"Trends Mol Med"},{"key":"2712_CR10","doi-asserted-by":"publisher","first-page":"615","DOI":"10.3233\/JAD-220908","volume":"92","author":"P Chatterjee","year":"2023","unstructured":"Chatterjee P, Dor\u00e9 V, Pedrini S, Krishnadas N, Thota R, Bourgeat P et al (2023) plasma glial fibrillary acidic protein is associated with 18F-SMBT-1 PET: two putative astrocyte reactivity biomarkers for Alzheimer\u2019s disease. J Alzheimers Dis JAD 92:615\u2013628. https:\/\/doi.org\/10.3233\/JAD-220908","journal-title":"J Alzheimers Dis JAD"},{"key":"2712_CR11","doi-asserted-by":"publisher","first-page":"e067715","DOI":"10.1002\/alz.067715","volume":"19","author":"K Chiotis","year":"2023","unstructured":"Chiotis K, Jelic V, Rodriguez-Vieitez E, Savitcheva I, Wall A, Antoni G et al (2023) Reactive astrocytes as imaged with 11C-DED in patients with different dementia disorders. Alzheimers Dement 19:e067715. https:\/\/doi.org\/10.1002\/alz.067715","journal-title":"Alzheimers Dement"},{"key":"2712_CR12","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13024-023-00647-y","volume":"18","author":"K Chiotis","year":"2023","unstructured":"Chiotis K, Johansson C, Rodriguez-Vieitez E, Ashton NJ, Blennow K, Zetterberg H et al (2023) Tracking reactive astrogliosis in autosomal dominant and sporadic Alzheimer\u2019s disease with multi-modal PET and plasma GFAP. Mol Neurodegener 18:60. https:\/\/doi.org\/10.1186\/s13024-023-00647-y","journal-title":"Mol Neurodegener"},{"key":"2712_CR13","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1038\/s41593-020-00735-y","volume":"23","author":"H Chun","year":"2020","unstructured":"Chun H, Im H, Kang YJ, Kim Y, Shin JH, Won W et al (2020) Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer\u2019s disease via H2O2\u2212 production. Nat Neurosci 23:1555\u20131566. https:\/\/doi.org\/10.1038\/s41593-020-00735-y","journal-title":"Nat Neurosci"},{"key":"2712_CR14","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s12974-020-01898-y","volume":"17","author":"S Das","year":"2020","unstructured":"Das S, Li Z, Noori A, Hyman BT, Serrano-Pozo A (2020) Meta-analysis of mouse transcriptomic studies supports a context-dependent astrocyte reaction in acute CNS injury versus neurodegeneration. J Neuroinflammation 17:227. https:\/\/doi.org\/10.1186\/s12974-020-01898-y","journal-title":"J Neuroinflammation"},{"key":"2712_CR15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/glia.440080208","volume":"8","author":"J Ekblom","year":"1993","unstructured":"Ekblom J, Jossan SS, Bergstr\u00fcm M, Oreland L, Walum E, Aquilonius S-M (1993) Monoamine oxidase-B in astrocytes: MAO-B in astrocytes. Glia 8:122\u2013132. https:\/\/doi.org\/10.1002\/glia.440080208","journal-title":"Glia"},{"key":"2712_CR16","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 et al (2021) Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci 24:312\u2013325. https:\/\/doi.org\/10.1038\/s41593-020-00783-4","journal-title":"Nat Neurosci"},{"key":"2712_CR17","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1016\/j.neurobiolaging.2008.11.006","volume":"31","author":"M Garcia-Alloza","year":"2010","unstructured":"Garcia-Alloza M, Borrelli LA, Hyman BT, Bacskai BJ (2010) Antioxidants have a rapid and long-lasting effect on neuritic abnormalities in APP:PS1 mice. Neurobiol Aging 31:2058\u20132068. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2008.11.006","journal-title":"Neurobiol Aging"},{"key":"2712_CR18","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1097\/01.jnen.0000240468.12543.af","volume":"65","author":"M Garcia-Alloza","year":"2006","unstructured":"Garcia-Alloza M, Dodwell SA, Meyer-Luehmann M, Hyman BT, Bacskai BJ (2006) Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model. J Neuropathol Exp Neurol 65:1082\u20131089. https:\/\/doi.org\/10.1097\/01.jnen.0000240468.12543.af","journal-title":"J Neuropathol Exp Neurol"},{"key":"2712_CR19","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/s12974-023-02869-9","volume":"20","author":"EF Garland","year":"2023","unstructured":"Garland EF, Dennett O, Lau LC, Chatelet DS, Bottlaender M, Nicoll JAR et al (2023) The mitochondrial protein TSPO in Alzheimer\u2019s disease: relation to the severity of AD pathology and the neuroinflammatory environment. J Neuroinflammation 20:186. https:\/\/doi.org\/10.1186\/s12974-023-02869-9","journal-title":"J Neuroinflammation"},{"key":"2712_CR20","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/bpa.12763","volume":"30","author":"Y Gui","year":"2020","unstructured":"Gui Y, Marks JD, Das S, Hyman BT, Serrano-Pozo A (2020) Characterization of the 18 kDa translocator protein (TSPO) expression in post-mortem normal and Alzheimer\u2019s disease brains. Brain Pathol 30:151\u2013164. https:\/\/doi.org\/10.1111\/bpa.12763","journal-title":"Brain Pathol"},{"key":"2712_CR21","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 et al (2011) Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-l-deprenyl using whole hemisphere autoradiography. Neurochem Int 58:60\u201368. https:\/\/doi.org\/10.1016\/j.neuint.2010.10.013","journal-title":"Neurochem Int"},{"key":"2712_CR22","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.2967\/jnumed.113.121020","volume":"54","author":"Q Guo","year":"2013","unstructured":"Guo Q, Colasanti A, Owen DR, Onega M, Kamalakaran A, Bennacef I et al (2013) Quantification of the specific translocator protein signal of 18F-PBR111 in healthy humans: a genetic polymorphism effect on in vivo binding. J Nucl Med 54:1915\u20131923. https:\/\/doi.org\/10.2967\/jnumed.113.121020","journal-title":"J Nucl Med"},{"key":"2712_CR23","doi-asserted-by":"publisher","first-page":"807435","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 (2022) Imaging of reactive astrogliosis by positron emission tomography. Front Neurosci 16:807435. https:\/\/doi.org\/10.3389\/fnins.2022.807435","journal-title":"Front Neurosci"},{"key":"2712_CR24","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00401-020-02175-1","volume":"140","author":"MD Ikonomovic","year":"2020","unstructured":"Ikonomovic MD, Buckley CJ, Abrahamson EE, Kofler JK, Mathis CA, Klunk WE et al (2020) Post-mortem analyses of PiB and flutemetamol in diffuse and cored amyloid-\u03b2 plaques in Alzheimer\u2019s disease. Acta Neuropathol (Berl) 140:463\u2013476. https:\/\/doi.org\/10.1007\/s00401-020-02175-1","journal-title":"Acta Neuropathol (Berl)"},{"key":"2712_CR25","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0165-5728(89)90115-x","volume":"24","author":"S Itagaki","year":"1989","unstructured":"Itagaki S, McGeer PL, Akiyama H, Zhu S, Selkoe D (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J Neuroimmunol 24:173\u2013182. https:\/\/doi.org\/10.1016\/0165-5728(89)90115-x","journal-title":"J Neuroimmunol"},{"key":"2712_CR26","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/nm.3639","volume":"20","author":"S Jo","year":"2014","unstructured":"Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH et al (2014) GABA from reactive astrocytes impairs memory in mouse models of Alzheimer\u2019s disease. Nat Med 20:886\u2013896. https:\/\/doi.org\/10.1038\/nm.3639","journal-title":"Nat Med"},{"key":"2712_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0306-4522(91)90098-9","volume":"45","author":"SS Jossan","year":"1991","unstructured":"Jossan SS, Gillberg PG, Gottfries CG, Karlsson I, Oreland L (1991) Monoamine oxidase B in brains from patients with Alzheimer\u2019s disease: a biochemical and autoradiographical study. Neuroscience 45:1\u201312. https:\/\/doi.org\/10.1016\/0306-4522(91)90098-9","journal-title":"Neuroscience"},{"key":"2712_CR28","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/jcbfm.2012.131","volume":"33","author":"WC Kreisl","year":"2013","unstructured":"Kreisl WC, Jenko KJ, Hines CS, Lyoo CH, Corona W, Morse CL et al (2013) A genetic polymorphism for translocator protein 18 Kda affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab 33:53\u201358. https:\/\/doi.org\/10.1038\/jcbfm.2012.131","journal-title":"J Cereb Blood Flow Metab"},{"key":"2712_CR29","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 (1982) Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci 79:6385\u20136389. https:\/\/doi.org\/10.1073\/pnas.79.20.6385","journal-title":"Proc Natl Acad Sci"},{"key":"2712_CR30","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.jalz.2019.03.016","volume":"15","author":"VJ Lowe","year":"2019","unstructured":"Lowe VJ, Lundt ES, Albertson SM, Przybelski SA, Senjem ML, Parisi JE et al (2019) Neuroimaging correlates with neuropathologic schemes in neurodegenerative disease. Alzheimers Dement J Alzheimers Assoc 15:927\u2013939. https:\/\/doi.org\/10.1016\/j.jalz.2019.03.016","journal-title":"Alzheimers Dement J Alzheimers Assoc"},{"key":"2712_CR31","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1177\/002215540004801206","volume":"48","author":"TW Mitchell","year":"2000","unstructured":"Mitchell TW, Nissanov J, Han LY, Mufson EJ, Schneider JA, Cochran EJ et al (2000) Novel method to quantify neuropil threads in brains from elders with or without cognitive impairment. J Histochem Cytochem Off J Histochem Soc 48:1627\u20131638. https:\/\/doi.org\/10.1177\/002215540004801206","journal-title":"J Histochem Cytochem Off J Histochem Soc"},{"key":"2712_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","volume":"123","author":"TJ Montine","year":"2012","unstructured":"Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW et al (2012) National Institute on Aging\u2013Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach. Acta Neuropathol (Berl) 123:1\u201311. https:\/\/doi.org\/10.1007\/s00401-011-0910-3","journal-title":"Acta Neuropathol (Berl)"},{"key":"2712_CR33","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.3233\/JAD-161309","volume":"58","author":"S Nave","year":"2017","unstructured":"Nave S, Doody RS, Boada M, Grimmer T, Savola J-M, Delmar P et al (2017) Sembragiline in moderate Alzheimer\u2019s Disease: results of a randomized, double-blind, placebo-controlled phase II trial (MAyflOwer RoAD). J Alzheimers Dis JAD 58:1217\u20131228. https:\/\/doi.org\/10.3233\/JAD-161309","journal-title":"J Alzheimers Dis JAD"},{"key":"2712_CR34","doi-asserted-by":"publisher","first-page":"5247","DOI":"10.1038\/s41467-023-40937-z","volume":"14","author":"E Nutma","year":"2023","unstructured":"Nutma E, Fancy N, Weinert M, Tsartsalis S, Marzin MC, Muirhead RCJ et al (2023) Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases. Nat Commun 14:5247. https:\/\/doi.org\/10.1038\/s41467-023-40937-z","journal-title":"Nat Commun"},{"key":"2712_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/jcbfm.2011.147","volume":"32","author":"DR Owen","year":"2012","unstructured":"Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A et al (2012) An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 32:1\u20135. https:\/\/doi.org\/10.1038\/jcbfm.2011.147","journal-title":"J Cereb Blood Flow Metab"},{"key":"2712_CR36","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-2507179\/v1","author":"T Pascoal","year":"2023","unstructured":"Pascoal T, Bellaver B, Povala G, Ferreira P, Ferrari-Souza JP, Leffa D et al (2023) Astrocyte reactivity influences the association of amyloid-\u03b2 and tau biomarkers in preclinical Alzheimer\u2019s disease. Res Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-2507179\/v1","journal-title":"Res Sq"},{"key":"2712_CR37","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1038\/s41591-021-01456-w","volume":"27","author":"TA Pascoal","year":"2021","unstructured":"Pascoal TA, Benedet AL, Ashton NJ, Kang MS, Therriault J, Chamoun M et al (2021) Microglial activation and tau propagate jointly across Braak stages. Nat Med 27:1592\u20131599. https:\/\/doi.org\/10.1038\/s41591-021-01456-w","journal-title":"Nat Med"},{"key":"2712_CR38","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fnagi.2018.00114","volume":"10","author":"BG Perez-Nievas","year":"2018","unstructured":"Perez-Nievas BG, Serrano-Pozo A (2018) Deciphering the astrocyte reaction in Alzheimer\u2019s disease. Front Aging Neurosci 10:114. https:\/\/doi.org\/10.3389\/fnagi.2018.00114","journal-title":"Front Aging Neurosci"},{"key":"2712_CR39","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/0014-4886(95)90022-5","volume":"132","author":"CJ Pike","year":"1995","unstructured":"Pike CJ, Cummings BJ, Cotman CW (1995) Early association of reactive astrocytes with senile plaques in Alzheimer\u2019s disease. Exp Neurol 132:172\u2013179. https:\/\/doi.org\/10.1016\/0014-4886(95)90022-5","journal-title":"Exp Neurol"},{"key":"2712_CR40","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/978-1-4939-7704-8_16","volume":"1750","author":"E Rodriguez-Vieitez","year":"2018","unstructured":"Rodriguez-Vieitez E, Nordberg A (2018) Imaging neuroinflammation: quantification of astrocytosis in a multitracer PET approach. Methods Mol Biol Clifton NJ 1750:231\u2013251. https:\/\/doi.org\/10.1007\/978-1-4939-7704-8_16","journal-title":"Methods Mol Biol Clifton NJ"},{"key":"2712_CR41","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 et al (2016) Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer\u2019s disease. Brain 139:922\u2013936. https:\/\/doi.org\/10.1093\/brain\/awv404","journal-title":"Brain"},{"key":"2712_CR42","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13195-017-0279-1","volume":"9","author":"S Schedin-Weiss","year":"2017","unstructured":"Schedin-Weiss S, Inoue M, Hromadkova L, Teranishi Y, Yamamoto NG, Wiehager B et al (2017) Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with \u03b3-secretase and regulates neuronal amyloid \u03b2-peptide levels. Alzheimers Res Ther 9:57. https:\/\/doi.org\/10.1186\/s13195-017-0279-1","journal-title":"Alzheimers Res Ther"},{"key":"2712_CR43","doi-asserted-by":"publisher","first-page":"16404","DOI":"10.1038\/srep16404","volume":"5","author":"M Sch\u00f6ll","year":"2015","unstructured":"Sch\u00f6ll M, Carter SF, Westman E, Rodriguez-Vieitez E, Almkvist O, Thordardottir S et al (2015) Early astrocytosis in autosomal dominant Alzheimer\u2019s disease measured in vivo by multi-tracer positron emission tomography. Sci Rep 5:16404. https:\/\/doi.org\/10.1038\/srep16404","journal-title":"Sci Rep"},{"key":"2712_CR44","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/j.ajpath.2011.05.047","volume":"179","author":"A Serrano-Pozo","year":"2011","unstructured":"Serrano-Pozo A, Mielke ML, G\u00f3mez-Isla T, Betensky RA, Growdon JH, Frosch MP et al (2011) Reactive glia not only associates with plaques but also parallels tangles in Alzheimer\u2019s disease. Am J Pathol 179:1373\u20131384. https:\/\/doi.org\/10.1016\/j.ajpath.2011.05.047","journal-title":"Am J Pathol"},{"key":"2712_CR45","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1097\/NEN.0b013e3182933788","volume":"72","author":"A Serrano-Pozo","year":"2013","unstructured":"Serrano-Pozo A, Muzikansky A, G\u00f3mez-Isla T, Growdon JH, Betensky RA, Frosch MP et al (2013) Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease. J Neuropathol Exp Neurol 72:462\u2013471. https:\/\/doi.org\/10.1097\/NEN.0b013e3182933788","journal-title":"J Neuropathol Exp Neurol"},{"key":"2712_CR46","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.2967\/jnumed.121.263255","volume":"63","author":"VL Villemagne","year":"2022","unstructured":"Villemagne VL, Harada R, Dor\u00e9 V, Furumoto S, Mulligan R, Kudo Y et al (2022) Assessing reactive astrogliosis with 18F-SMBT-1 across the Alzheimer disease spectrum. J Nucl Med 63:1560\u20131569. https:\/\/doi.org\/10.2967\/jnumed.121.263255","journal-title":"J Nucl Med"},{"key":"2712_CR47","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.2967\/jnumed.121.263254","volume":"63","author":"VL Villemagne","year":"2022","unstructured":"Villemagne VL, Harada R, Dor\u00e9 V, Furumoto S, Mulligan R, Kudo Y et al (2022) First-in-humans evaluation of 18F-SMBT-1, a Novel 18F-labeled monoamine oxidase-B PET tracer for imaging reactive astrogliosis. J Nucl Med 63:1551\u20131559. https:\/\/doi.org\/10.2967\/jnumed.121.263254","journal-title":"J Nucl Med"},{"key":"2712_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/alz.039858","author":"VL Villemagne","year":"2020","unstructured":"Villemagne VL, Harada R, Dore V, Furumoto S, Mulligan RS, Kudo Y et al (2020) Evaluation of the novel 18F-labeled PET tracer SMBT-1 for imaging astrogliosis in healthy elderly controls and A+\/T+\/(N+) Alzheimer\u2019s disease patients: neuroimaging: novel imaging methods. Alzheimers Dement. https:\/\/doi.org\/10.1002\/alz.039858","journal-title":"Alzheimers Dement"},{"key":"2712_CR49","doi-asserted-by":"publisher","first-page":"4159","DOI":"10.1038\/ncomms5159","volume":"5","author":"Z Wu","year":"2014","unstructured":"Wu Z, Guo Z, Gearing M, Chen G (2014) Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer\u2019s (corrected) disease model. Nat Commun 5:4159. https:\/\/doi.org\/10.1038\/ncomms5159","journal-title":"Nat Commun"},{"key":"2712_CR50","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1002\/stem.2831","volume":"36","author":"L Yin","year":"2018","unstructured":"Yin L, Li J, Liao C-P, Jason WuB (2018) Monoamine oxidase deficiency causes prostate atrophy and reduces prostate progenitor cell activity. Stem Cells Dayt Ohio 36:1249\u20131258. https:\/\/doi.org\/10.1002\/stem.2831","journal-title":"Stem Cells Dayt Ohio"},{"key":"2712_CR51","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.2967\/jnumed.112.118885","volume":"54","author":"KK Yoder","year":"2013","unstructured":"Yoder KK, Nho K, Risacher SL, Kim S, Shen L, Saykin AJ (2013) Influence of TSPO genotype on 11C-PBR28 standardized uptake values. J Nucl Med 54:1320\u20131322. https:\/\/doi.org\/10.2967\/jnumed.112.118885","journal-title":"J Nucl Med"},{"key":"2712_CR52","doi-asserted-by":"publisher","first-page":"4951","DOI":"10.1113\/jphysiol.2014.278754","volume":"592","author":"B-E Yoon","year":"2014","unstructured":"Yoon B-E, Woo J, Chun Y-E, Chun H, Jo S, Bae JY et al (2014) Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. J Physiol 592:4951\u20134968. https:\/\/doi.org\/10.1113\/jphysiol.2014.278754","journal-title":"J Physiol"},{"key":"2712_CR53","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nrn1883","volume":"7","author":"MBH Youdim","year":"2006","unstructured":"Youdim MBH, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7:295\u2013309. https:\/\/doi.org\/10.1038\/nrn1883","journal-title":"Nat Rev Neurosci"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-024-02712-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-024-02712-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-024-02712-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T14:04:16Z","timestamp":1712153056000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-024-02712-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["2712"],"URL":"https:\/\/doi.org\/10.1007\/s00401-024-02712-2","relation":{},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]},"assertion":[{"value":"20 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"66"}}