TY - JOUR
T1 - Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease
AU - the DELCODE study group
AU - Brosseron, Frederic
AU - Maass, Anne
AU - Kleineidam, Luca
AU - Ravichandran, Kishore Aravind
AU - González, Pablo García
AU - McManus, Róisín M.
AU - Ising, Christina
AU - Santarelli, Francesco
AU - Kolbe, Carl Christian
AU - Häsler, Lisa M.
AU - Wolfsgruber, Steffen
AU - Marquié, Marta
AU - Boada, Mercè
AU - Orellana, Adelina
AU - de Rojas, Itziar
AU - Röske, Sandra
AU - Peters, Oliver
AU - Cosma, Nicoleta Carmen
AU - Cetindag, Arda
AU - Wang, Xiao
AU - Priller, Josef
AU - Spruth, Eike J.
AU - Altenstein, Slawek
AU - Schneider, Anja
AU - Fliessbach, Klaus
AU - Wiltfang, Jens
AU - Schott, Björn H.
AU - Bürger, Katharina
AU - Janowitz, Daniel
AU - Dichgans, Martin
AU - Perneczky, Robert
AU - Rauchmann, Boris Stephan
AU - Teipel, Stefan
AU - Kilimann, Ingo
AU - Goerss, Doreen
AU - Laske, Christoph
AU - Munk, Matthias H.
AU - Düzel, Emrah
AU - Yakupov, Renat
AU - Dobisch, Laura
AU - Metzger, Coraline D.
AU - Glanz, Wenzel
AU - Ewers, Michael
AU - Dechent, Peter
AU - Haynes, John Dylan
AU - Scheffler, Klaus
AU - Roy, Nina
AU - Rostamzadeh, Ayda
AU - Teunissen, Charlotte E.
AU - Marchant, Natalie L.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/3/16
Y1 - 2022/3/16
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - TAM receptor
KW - biomarker
KW - neuroinflammation
UR - https://www.scopus.com/pages/publications/85126306517
U2 - 10.1016/j.neuron.2021.12.016
DO - 10.1016/j.neuron.2021.12.016
M3 - Article
C2 - 34995486
AN - SCOPUS:85126306517
SN - 0896-6273
VL - 110
SP - 1009-1022.e4
JO - Neuron
JF - Neuron
IS - 6
ER -