Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases

ABSTRACT

Introduction: Neuroinflammation is a crucial mechanism in the pathophysiology of neurodegenerative diseases pathophysiology. Cerebrospinal fluid (CSF) YKL-40 – an indicator of microglial activation − has recently been identified by proteomic studies as a candidate biomarker for Alzheimer’s disease (AD).

Areas covered: We review the impact of CSF YKL-40 as a pathophysiological biomarker for AD and other neurodegenerative diseases. CSF YKL-40 concentrations have been shown to predict progression from prodromal mild cognitive impairment to AD dementia. Moreover, a positive association between CSF YKL-40 and other biomarkers of neurodegeneration – particularly total tau protein − has been reported during the asymptomatic preclinical stage of AD and other neurodegenerative diseases. Albeit preliminary, current data do not support an association between APOE-ε4 status and CSF YKL-40 concentrations. When interpreting the diagnostic/prognostic significance of CSF YKL-40 concentrations in neurodegenerative diseases, potential confounders – including age, metabolic and cardiovascular risk factors, diagnostic criteria for selecting cases/controls – need to be considered.

Expert opinion/commentary: CSF YKL-40 represents a pathophysiological biomarker reflecting immune/inflammatory mechanisms in neurodegenerative diseases, associated with tau protein pathology. Besides being associated with tau pathology, CSF YKL-40 adds to the growing array of biomarkers reflecting distinct molecular brain mechanisms potentially useful for stratifying individuals for biomarker-guided, targeted anti-inflammatory therapies emerging from precision medicine.

KEYWORDS:

• YKL-40
• neuroinflammation
• biomarkers
• cerebrospinal fluid
• Alzheimer’s disease
• mild cognitive impairment
• dementia
• neurodegenerative diseases

Declaration of interest

S Lista has received lecture honoraria from Roche. U Bonuccelli has received fees for consultation from GSK and Eisai and for speeches from Novartis, GSK, and Lundbeck. H Hampel declares no competing financial interests related to the present article. He serves as Senior Associate Editor for the journal Alzheimer’s & Dementia®; he has been a scientific consultant and/or speaker and/or attended scientific advisory boards of Axovant, Anavex, Eli Lilly and company, GE Healthcare, Cytox, Jung Diagnostics, Roche, Biogen Idec, Takeda-Zinfandel, Oryzon Genomics, Qynapse; and receives research support from the Association for Alzheimer Research (Paris), Pierre and Marie Curie University (Paris), Pfizer & Avid (paid to institution); and has patents as co-inventor, but received no royalties: A patent in vitro multiparameter determination method for the Diagnosis and early diagnosis of neurodegenerative disorders. Patent number: 8916388 Issued. A patent in vitro procedure for diagnosis and early diagnosis of neurodegenerative diseases. Patent number: 8298784 Issued. A patent Neurodegenerative Markers for Psychiatric Conditions. Publication number: 20120196300 Issued. A patent IN VITRO MULTIPARAMETER DETERMINATION METHOD FOR THE DIAGNOSIS AND EARLY DIAGNOSIS OF NEURODEGENERATIVE DISORDERS. Publication number: 20100062463 Issued. A patent IN VITRO METHOD FOR THE DIAGNOSIS AND EARLY DIAGNOSIS OF NEURODEGENERATIVE DISORDERS. Publication number: 20100035286 Issued. A patent In vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases. Publication number: 20090263822 Issued. A patent in vitro method for the diagnosis of neurodegenerative diseases. Patent number: 7547553 Issued. A patent CSF Diagnostic in Vitro Method for Diagnosis of Dementias and Neuroinflammatory Diseases. Publication number: 20080206797 Issued. A patent in vitro Method For the Diagnosis of Neurodegenerative Diseases. Publication number: 20080199966 Issued. A patent Neurodegenerative Markers for Psychiatric Conditions. Publication number: 20080131921 Issued. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the AXA Research Fund, the “Fondation Université Pierre et Marie Curie” and the “Fondation pour La Recherche sur Alzheimer”, Paris, France. Ce travail a bénéficié d’une aide de l’Etat “Investissements d’avenir” ANR-10-IAIHU-06 (Harald Hampel). The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6) (Harald Hampel).