Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease.

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.

• Authors: Frederic Brosseron, Anne Maass, Luca Kleineidam, Kishore Aravind Ravichandran, Pablo García González, Róisín M McManus, Christina Ising, Francesco Santarelli, Carl-Christian Kolbe, Lisa M Häsler, Steffen Wolfsgruber, Marta Marquié, Mercè Boada, Adelina Orellana, Itziar de Rojas, Sandra Röske, Oliver Peters, Nicoleta-Carmen Cosma, Arda Cetindag, Xiao Wang, Josef Priller, Eike J Spruth, Slawek Altenstein, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Björn H Schott, Katharina Bürger, Daniel Janowitz, Martin Dichgans, Robert Perneczky, Boris-Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H Munk, Emrah Düzel, Renat Yakupov, Laura Dobisch, Coraline D Metzger, Wenzel Glanz, Michael Ewers, Peter Dechent, John Dylan Haynes, Klaus Scheffler, Nina Roy, Ayda Rostamzadeh, Charlotte E Teunissen, Natalie L Marchant, Annika Spottke, Mathias Jucker, Eicke Latz, Michael Wagner, David Mengel, Matthis Synofzik, Frank Jessen, Alfredo Ramirez, Agustín Ruiz, Michael T Heneka, DELCODE study group
• Journal: Neuron (Neuron) Vol. 110 Issue 6 Pg. 1009-1022.e4 (03 16 2022) ISSN: 1097-4199 [Electronic] United States
• PMID: 34995486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• tau Proteins

Topics

• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides
• Biomarkers (cerebrospinal fluid)
• Cognitive Dysfunction
• Cohort Studies
• Humans
• Inflammation (metabolism)
• tau Proteins (cerebrospinal fluid)