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

Alzheimer Disease/metabolism; Amyloid beta-Peptides; Biomarkers/cerebrospinal fluid; Cognitive Dysfunction; Cohort Studies; Humans; Inflammation/metabolism; tau Proteins/cerebrospinal fluid; Alzheimer's disease; TAM receptor; biomarker; neuroinflammation

Abstract :

[en] 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.

Disciplines :

Neurology

Author, co-author :

Brosseron, Frederic

Maass, Anne

Kleineidam, Luca

Ravichandran, Kishore Aravind

González, Pablo García

McManus, Róisín M.

Ising, Christina

Santarelli, Francesco

Kolbe, Carl-Christian

Häsler, Lisa M.

More authors (50 more)

External co-authors :

yes

Language :

English

Title :

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

Publication date :

2022

Journal title :

Neuron

ISSN :

1097-4199

Publisher :

Cell Press, Cambridge, United States - Massachusetts

Volume :

110

Issue :

Pages :

1009-1022.e4

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBilu :

since 26 January 2023

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