eprintid: 10147406 rev_number: 10 eprint_status: archive userid: 699 dir: disk0/10/14/74/06 datestamp: 2022-04-27 15:43:53 lastmod: 2023-01-07 07:10:37 status_changed: 2022-04-27 15:43:53 type: article metadata_visibility: show sword_depositor: 699 creators_name: Brosseron, Frederic creators_name: Maass, Anne creators_name: Kleineidam, Luca creators_name: Ravichandran, Kishore Aravind creators_name: Gonzalez, Pablo Garcia creators_name: McManus, Roisin M creators_name: Ising, Christina creators_name: Santarelli, Francesco creators_name: Kolbe, Carl-Christian creators_name: Haesler, Lisa M creators_name: Wolfsgruber, Steffen creators_name: Marquie, Marta creators_name: Boada, Merce creators_name: Orellana, Adelina creators_name: de Rojas, Itziar creators_name: Roeske, Sandra creators_name: Peters, Oliver creators_name: Cosma, Nicoleta-Carmen creators_name: Cetindag, Arda creators_name: Wang, Xiao creators_name: Priller, Josef creators_name: Spruth, Eike J creators_name: Altenstein, Slawek creators_name: Schneider, Anja creators_name: Fliessbach, Klaus creators_name: Wiltfang, Jens creators_name: Schott, Bjorn H creators_name: Buerger, Katharina creators_name: Janowitz, Daniel creators_name: Dichgans, Martin creators_name: Perneczky, Robert creators_name: Rauchmann, Boris-Stephan creators_name: Teipel, Stefan creators_name: Kilimann, Ingo creators_name: Goerss, Doreen creators_name: Laske, Christoph creators_name: Munk, Matthias H creators_name: Duzel, Emrah creators_name: Yakupov, Renat creators_name: Dobisch, Laura creators_name: Metzger, Coraline D creators_name: Glanz, Wenzel creators_name: Ewers, Michael creators_name: Dechent, Peter creators_name: Haynes, John Dylan creators_name: Scheffler, Klaus creators_name: Roy, Nina creators_name: Rostamzadeh, Ayda creators_name: Teunissen, Charlotte E creators_name: Marchant, Natalie L creators_name: Spottke, Annika creators_name: Jucker, Mathias creators_name: Latz, Eicke creators_name: Wagner, Michael creators_name: Mengel, David creators_name: Synofzik, Matthis creators_name: Jessen, Frank creators_name: Ramirez, Alfredo creators_name: Ruiz, Agustin creators_name: Heneka, Michael T title: Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease ispublished: pub divisions: C07 divisions: D79 divisions: B02 divisions: UCL divisions: F69 divisions: D05 keywords: Alzheimer's disease; neuroinflammation; biomarker; TAM receptor note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. abstract: There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona. We investigated whether respective biomarker changes are evident before onset of cognitive impairment. YKL-40; sTREM2; sAXL; sTyro3; MIF; complement factors C1q, C4, and H; ferritin; and ApoE protein were elevated in pre-dementia subjects with pathological levels of tau or other neurodegeneration markers, demonstrating tight interactions between inflammation and accumulating neurodegeneration even before onset of symptoms. Intriguingly, higher levels of ApoE and soluble TAM receptors sAXL and sTyro3 were related to larger brain structure and stable cognitive outcome at follow-up. Our findings indicate a protective mechanism relevant for intervention strategies aiming to regulate neuroinflammation in subjects with no or subjective symptoms but underlying AD pathology profile. date: 2022-03-16 date_type: published publisher: CELL PRESS official_url: https://doi.org/10.1016/j.neuron.2021.12.016 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1913973 doi: 10.1016/j.neuron.2021.12.016 medium: Print-Electronic pii: S0896-6273(21)01033-3 lyricists_name: Marchant, Natalie lyricists_name: Duzel, Emrah lyricists_id: NLMAR24 lyricists_id: EDUZE48 actors_name: Marchant, Natalie actors_id: NLMAR24 actors_role: owner funding_acknowledgements: [German Center for Neurodegenerative Diseases (DZNE e.V.) within the Helmholtz Association]; 01ED2007B [PREADAPT project within the EU Joint Programs for Neurodegenerative Diseases Research (JPND) PERSOMED]; 01ED1619A [PREADAPT project within the JPND PERSOMED (German Federal Ministry of Education and Research [BMBF] grant]; MR/T046171/1 [Medical Research Council within the JPND PERSOMED (PREADAPT project)]; FI20/00215 [Instituto de Salud Carlos III (ISCIII)]; [Grifols SA]; [Fundacion bancaria La Caixa]; [Fundacia ACE]; [CIBERNED]; 115975 [European Union/EFPIA Innovative Medicines Initiative joint undertaking ADAPTED project]; 115985 [European Union/EFPIA Innovative Medicines Initiative joint undertaking MOPEAD project]; [ISCIII-Subdireccion General de Evaluacion]; [Fondo Europeo de Desarrollo Regional (FEDER-`Una manera de hacer Europa')]; [JPco-fuND2 "Multinational research projects on Personalised Medicine for Neurodegenerative Diseases'']; AC19/00097 [PREADAPT project (ISCIII grant)]; AC17/00100 [EURONANOMED III Joint Transnational call]; [JPND grant "GENFI-prox'' (by DLR/BMBF)]; [European Union]; [State of Saxony-Anhalt (Research Alliance "Autonomy in Old Age'')]; PI13/02434 []; PI16/01861 []; PI17/01474 []; PI19/01240 []; PI19/01301 [] full_text_status: public publication: Neuron volume: 110 number: 6 pagerange: 1009-1022 pages: 19 event_location: United States issn: 0896-6273 citation: Brosseron, Frederic; Maass, Anne; Kleineidam, Luca; Ravichandran, Kishore Aravind; Gonzalez, Pablo Garcia; McManus, Roisin M; Ising, Christina; ... Heneka, Michael T; + view all <#> Brosseron, Frederic; Maass, Anne; Kleineidam, Luca; Ravichandran, Kishore Aravind; Gonzalez, Pablo Garcia; McManus, Roisin M; Ising, Christina; Santarelli, Francesco; Kolbe, Carl-Christian; Haesler, Lisa M; Wolfsgruber, Steffen; Marquie, Marta; Boada, Merce; Orellana, Adelina; de Rojas, Itziar; Roeske, Sandra; Peters, Oliver; Cosma, Nicoleta-Carmen; Cetindag, Arda; Wang, Xiao; Priller, Josef; Spruth, Eike J; Altenstein, Slawek; Schneider, Anja; Fliessbach, Klaus; Wiltfang, Jens; Schott, Bjorn H; Buerger, Katharina; Janowitz, Daniel; Dichgans, Martin; Perneczky, Robert; Rauchmann, Boris-Stephan; Teipel, Stefan; Kilimann, Ingo; Goerss, Doreen; Laske, Christoph; Munk, Matthias H; Duzel, Emrah; Yakupov, Renat; Dobisch, Laura; Metzger, Coraline D; Glanz, Wenzel; Ewers, Michael; Dechent, Peter; Haynes, John Dylan; Scheffler, Klaus; Roy, Nina; Rostamzadeh, Ayda; Teunissen, Charlotte E; Marchant, Natalie L; Spottke, Annika; Jucker, Mathias; Latz, Eicke; Wagner, Michael; Mengel, David; Synofzik, Matthis; Jessen, Frank; Ramirez, Alfredo; Ruiz, Agustin; Heneka, Michael T; - view fewer <#> (2022) Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease. Neuron , 110 (6) pp. 1009-1022. 10.1016/j.neuron.2021.12.016 <https://doi.org/10.1016/j.neuron.2021.12.016>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10147406/2/Marchant_Brosseron_Maass_Kleineidam_20211210.pdf