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

Brosseron, Frederic; Maass, Anne; Kleineidam, Luca; Ravichandran, Kishore Aravind; Gonzalez, Pablo Garcia; McManus, Roisin M; Ising, Christina; ... Heneka, Michael T; + view all (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.

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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.

Type: Article
Title: Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease
Location: United States
DOI: 10.1016/j.neuron.2021.12.016
Publisher version: https://doi.org/10.1016/j.neuron.2021.12.016
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Alzheimer's disease; neuroinflammation; biomarker; TAM receptor
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10147406
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