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. 2022 Mar 16;110(6):1009-1022.e4.
doi: 10.1016/j.neuron.2021.12.016. Epub 2022 Jan 6.

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

Frederic Brosseron  1 , Anne Maass  2 , Luca Kleineidam  1 , Kishore Aravind Ravichandran  1 , Pablo García González  3 , Róisín M McManus  1 , Christina Ising  1 , Francesco Santarelli  1 , Carl-Christian Kolbe  4 , Lisa M Häsler  5 , Steffen Wolfsgruber  1 , Marta Marquié  3 , Mercè Boada  3 , Adelina Orellana  3 , Itziar de Rojas  3 , Sandra Röske  6 , Oliver Peters  7 , Nicoleta-Carmen Cosma  7 , Arda Cetindag  7 , Xiao Wang  8 , Josef Priller  9 , Eike J Spruth  7 , Slawek Altenstein  7 , Anja Schneider  1 , Klaus Fliessbach  1 , Jens Wiltfang  10 , Björn H Schott  11 , Katharina Bürger  12 , Daniel Janowitz  13 , Martin Dichgans  12 , Robert Perneczky  14 , Boris-Stephan Rauchmann  13 , Stefan Teipel  15 , Ingo Kilimann  15 , Doreen Goerss  16 , Christoph Laske  17 , Matthias H Munk  17 , Emrah Düzel  18 , Renat Yakupov  2 , Laura Dobisch  18 , Coraline D Metzger  19 , Wenzel Glanz  2 , Michael Ewers  20 , Peter Dechent  21 , John Dylan Haynes  22 , Klaus Scheffler  23 , Nina Roy  24 , Ayda Rostamzadeh  25 , Charlotte E Teunissen  26 , Natalie L Marchant  27 , Annika Spottke  28 , Mathias Jucker  5 , Eicke Latz  29 , Michael Wagner  1 , David Mengel  30 , Matthis Synofzik  30 , Frank Jessen  31 , Alfredo Ramirez  32 , Agustín Ruiz  3 , Michael T Heneka  33 ; DELCODE study group
Affiliations

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

Frederic Brosseron et al. Neuron. .

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.

Keywords: Alzheimer's disease; TAM receptor; biomarker; neuroinflammation.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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