TY - JOUR
T1 - Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
AU - INSIGHT-preAD study group and the Alzheimer Precision Medicine Initiative (APMI)
AU - INSIGHT-preAD Study Group
AU - Alzheimer Precision Medicine Initiative (APMI)
AU - Vergallo, Andrea
AU - Lista, Simone
AU - Lemercier, Pablo
AU - Chiesa, Patrizia A.
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Potier, Marie Claude
AU - Habert, Marie Odile
AU - Baldacci, Filippo
AU - Cavedo, Enrica
AU - Caraci, Filippo
AU - Dubois, Bruno
AU - Hampel, Harald
AU - Bakardjian, Hovagim
AU - Benali, Habib
AU - Bertin, Hugo
AU - Bonheur, Joel
AU - Boukadida, Laurie
AU - Boukerrou, Nadia
AU - Chiesa, Patrizia
AU - Colliot, Olivier
AU - Dubois, Marion
AU - Epelbaum, Stéphane
AU - Gagliardi, Geoffroy
AU - Genthon, Remy
AU - Houot, Marion
AU - Kas, Aurélie
AU - Lamari, Foudil
AU - Levy, Marcel
AU - Metzinger, Christiane
AU - Mochel, Fanny
AU - Nyasse, Francis
AU - Poisson, Catherine
AU - Revillon, Marie
AU - Santos, Antonio
AU - Andrade, Katia Santos
AU - Sole, Marine
AU - Surtee, Mohmed
AU - de Schotten, Michel Thiebaut
AU - Younsi, Nadjia
AU - Afshar, Mohammad
AU - Aguilar, Lisi Flores
AU - Akman-Anderson, Leyla
AU - Arenas, Joaquín
AU - Ávila, Jesús
AU - Babiloni, Claudio
AU - Batrla, Richard
AU - Benda, Norbert
AU - Black, Keith L.
AU - O'bryant, Sid E.
N1 - Funding Information:
INSIGHT-preAD study group: Hovagim Bakardjian, Habib Benali, Hugo Bertin, Joel Bonheur, Laurie Boukadida, Nadia Boukerrou, Enrica Cavedo, Patrizia Chiesa, Olivier Colliot, Bruno Dubois, Marion Dubois, Stéphane Epelbaum, Geoffroy Gagliardi, Remy Genthon, Marie-Odile Habert, Harald Hampel, Marion Houot, Aurélie Kas, Foudil Lamari, Marcel Levy, Simone Lista, Christiane Metzinger, Fanny Mochel, Francis Nyasse, Catherine Poisson, Marie-Claude Potier, Marie Revillon, Antonio Santos, Katia Santos Andrade, Marine Sole, Mohmed Surtee, Michel Thiebaut de Schotten, Andrea Vergallo, Nadjia Younsi. AV is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council (#2018–02532), the European Research Council (#681712), and Swedish State Support for Clinical Research (#ALFGBG-720931), as well as the UK Dementia Research Institute at UCL. KB holds the Torsten Söderberg Professorship of Medicine and is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and a grant (#ALFGBG-715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement. HH is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. At Sorbonne University he was supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Université” and the “Fondation pour la Recherche sur Alzheimer”, Paris, France.
Funding Information:
The research and this manuscript was part of the translational research program “PHOENIX,” awarded to HH, and administered by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer.
Funding Information:
CATI is a French neuroimaging platform funded by the French Plan Alzheimer (available at http://cati-neuroimaging.com ).
Funding Information:
The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received support within the “ Investissement d'Avenir ” ( ANR-10-AIHU-06 ) French program. The study was promoted in collaboration with the "CHU de Bordeaux" (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly.
Funding Information:
The research and this manuscript was part of the translational research program ?PHOENIX,? awarded to HH, and administered by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received support within the ?Investissement d'Avenir? (ANR-10-AIHU-06) French program. The study was promoted in collaboration with the ?CHU de Bordeaux? (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. CATI is a French neuroimaging platform funded by the French Plan Alzheimer (available at http://cati-neuroimaging.com).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid
KW - Neuroinflammation
KW - Sex
KW - YKL-40
UR - http://www.scopus.com/inward/record.url?scp=85092032708&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2020.07.009
DO - 10.1016/j.neurobiolaging.2020.07.009
M3 - Article
C2 - 32920471
AN - SCOPUS:85092032708
SN - 0197-4580
VL - 96
SP - 22
EP - 32
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -