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Publication Detail
Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease
  • Publication Type:
    Journal article
  • Authors:
    Brosseron F, Maass A, Kleineidam L, Ravichandran KA, Gonzalez PG, McManus RM, Ising C, Santarelli F, Kolbe C-C, Haesler LM, Wolfsgruber S, Marquie M, Boada M, Orellana A, de Rojas I, Roeske S, Peters O, Cosma N-C, Cetindag A, Wang X, Priller J, Spruth EJ, Altenstein S, Schneider A, Fliessbach K, Wiltfang J, Schott BH, Buerger K, Janowitz D, Dichgans M, Perneczky R, Rauchmann B-S, Teipel S, Kilimann I, Goerss D, Laske C, Munk MH, Duzel 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
  • Publisher:
    CELL PRESS
  • Publication date:
    16/03/2022
  • Pagination:
    1009, 1022
  • Journal:
    Neuron
  • Volume:
    110
  • Issue:
    6
  • Medium:
    Print-Electronic
  • Status:
    Published
  • Country:
    United States
  • Print ISSN:
    0896-6273
  • PII:
    S0896-6273(21)01033-3
  • Language:
    English
  • Keywords:
    Alzheimer's disease, neuroinflammation, biomarker, TAM receptor
  • Notes:
    This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
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.
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Institute of Cognitive Neuroscience
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Mental Health of Older People
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