Munich Cluster for Systems Neurology
print


Breadcrumb Navigation


Content

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

Neuron. 2021 Dec 31:S0896-6273(21)01033-3. doi: 10.1016/j.neuron.2021.12.016. Epub ahead of print. PMID: 34995486.

Authors/Editors: Brosseron F, Maass A, Kleineidam L, Ravichandran KA, González PG, McManus RM, Ising C, Santarelli F, Kolbe CC, Häsler LM, Wolfsgruber S, Marquié M, Boada M, Orellana A, de Rojas I, Röske S, Peters O, Cosma NC, Cetindag A, Wang X, Priller J, Spruth EJ, Altenstein S, Schneider A, Fliessbach K, Wiltfang J, Schott BH, Bürger K, Janowitz D, Dichgans M, Perneczky R, Rauchmann BS, Teipel S, Kilimann I, Göerß D, Laske C, Munk MH, Düzel E, Yakupov R, Dobisch L, Metzger CD, Glanz W, Ewers M, Dechent P, Haynes JD, Scheffler K, Roy N, Rostamzadeh A, Teunissen CE, Marchant NL, Spottke A, Jucker M, Latz E, Wagner M, Mengel D, Synofzik M, Jessen F, Ramirez A, Ruiz A, Heneka MT; DELCODE study group.
Publication Date: 2021

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.

Related Links