Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers

Vergallo, A.; Lista, S.; Lemercier, P.; Chiesa, P. A.; Zetterberg, H.; Blennow, K.; Potier, M. -C.; Habert, M. -O.; Baldacci, F.; Cavedo, E.; Caraci, F.; Dubois, B.; Hampel, H.; Bakardjian, H.; Benali, H.; Bertin, H.; Bonheur, J.; Boukadida, L.; Boukerrou, N.; Chiesa, P.; Colliot, O.; Dubois, M.; Epelbaum, S.; Gagliardi, G.; Genthon, R.; Houot, M.; Kas, A.; Lamari, F.; Levy, M.; Metzinger, C.; Mochel, F.; Nyasse, F.; Poisson, C.; Revillon, M.; Santos, A.; Andrade, K. S.; Sole, M.; Surtee, M.; de Schotten, M. T.; Younsi, N.; Afshar, M.; Aguilar, L. F.; Akman-Anderson, L.; Arenas, J.; Avila, J.; Babiloni, C.; Batrla, R.; Benda, N.; Black, K. L.; Bokde, A. L. W.; Bonuccelli, U.; Broich, K.; Cacciola, F.; Caruso, G.; Castrillo, J.; Ceravolo, R.; Corbo, M.; Corvol, J. -C.; Cuello, A. C.; Cummings, J. L.; Depypere, H.; Duggento, A.; Emanuele, E.; Escott-Price, V.; Federoff, H.; Ferretti, M. T.; Fiandaca, M.; Frank, R. A.; Garaci, F.; Geerts, H.; Giacobini, E.; Giorgi, F. S.; Goetzl, E. J.; Graziani, M.; Haberkamp, M.; Hanisch, B.; Herholz, K.; Hernandez, F.; Imbimbo, B. P.; Kapogiannis, D.; Karran, E.; Kiddle, S. J.; Kim, S. H.; Koronyo, Y.; Koronyo-Hamaoui, M.; Langevin, T.; Lehericy, S.; Llavero, F.; Lorenceau, J.; Lucia, A.; Mango, D.; Mapstone, M.; Neri, C.; Nistico, R.; O'Bryant, S. E.; Palermo, G.; Perry, G.; Ritchie, C.; Rossi, S.; Saidi, A.; Santarnecchi, E.; Schneider, L. S.; Sporns, O.; Toschi, N.; Valenzuela, P. L.; Vellas, B.; Verdooner, S. R.; Villain, N.; Giudici, K. V.; Watling, M.; Welikovitch, L. A.; Woodcock, J.; Younesi, E.; Zugaza, J. L.

doi:10.1016/j.neurobiolaging.2020.07.009

Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis.

Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers / Vergallo, A.; Lista, S.; Lemercier, P.; Chiesa, P. A.; Zetterberg, H.; Blennow, K.; Potier, M. -C.; Habert, M. -O.; Baldacci, F.; Cavedo, E.; Caraci, F.; Dubois, B.; Hampel, H.; Bakardjian, H.; Benali, H.; Bertin, H.; Bonheur, J.; Boukadida, L.; Boukerrou, N.; Chiesa, P.; Colliot, O.; Dubois, M.; Epelbaum, S.; Gagliardi, G.; Genthon, R.; Houot, M.; Kas, A.; Lamari, F.; Levy, M.; Metzinger, C.; Mochel, F.; Nyasse, F.; Poisson, C.; Revillon, M.; Santos, A.; Andrade, K. S.; Sole, M.; Surtee, M.; de Schotten, M. T.; Younsi, N.; Afshar, M.; Aguilar, L. F.; Akman-Anderson, L.; Arenas, J.; Avila, J.; Babiloni, C.; Batrla, R.; Benda, N.; Black, K. L.; Bokde, A. L. W.; Bonuccelli, U.; Broich, K.; Cacciola, F.; Caruso, G.; Castrillo, J.; Ceravolo, R.; Corbo, M.; Corvol, J. -C.; Cuello, A. C.; Cummings, J. L.; Depypere, H.; Duggento, A.; Emanuele, E.; Escott-Price, V.; Federoff, H.; Ferretti, M. T.; Fiandaca, M.; Frank, R. A.; Garaci, F.; Geerts, H.; Giacobini, E.; Giorgi, F. S.; Goetzl, E. J.; Graziani, M.; Haberkamp, M.; Hanisch, B.; Herholz, K.; Hernandez, F.; Imbimbo, B. P.; Kapogiannis, D.; Karran, E.; Kiddle, S. J.; Kim, S. H.; Koronyo, Y.; Koronyo-Hamaoui, M.; Langevin, T.; Lehericy, S.; Llavero, F.; Lorenceau, J.; Lucia, A.; Mango, D.; Mapstone, M.; Neri, C.; Nistico, R.; O'Bryant, S. E.; Palermo, G.; Perry, G.; Ritchie, C.; Rossi, S.; Saidi, A.; Santarnecchi, E.; Schneider, L. S.; Sporns, O.; Toschi, N.; Valenzuela, P. L.; Vellas, B.; Verdooner, S. R.; Villain, N.; Giudici, K. V.; Watling, M.; Welikovitch, L. A.; Woodcock, J.; Younesi, E.; Zugaza, J. L.. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 96:(2020), pp. 22-32. [10.1016/j.neurobiolaging.2020.07.009]