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

Abstract

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.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a pro-inflammatory glycoprotein expressed in differentiated glial cells, and is considered a marker of neuroinflammation [ 81 , 82 ]. Recently, serum levels of YKL-40 have been shown to be a promising marker for early MCI diagnosis and patient selection, as it is capable of discriminating between cognitive normality and mild cognitive impairment with 85% sensitivity and specificity.…”

“…Results from a multicentre study have shown that plasma YKL-40 concentration is higher in AD-related dementia, similar to what has been observed with YKL-40 in the CSF [ 82 ]. However, it should be noted that high levels of blood YKL-40 have also been reported in aging, vascular dementia, frontotemporal dementia, sporadic Creutzfeldt–Jakob disease, and Lewy body dementia, as well as to vary according to sex, thus almost excluding its applicability as a specific and differential AD biomarker [ 81 , 85 ].…”

Inflammatory plasma biomarkers in subjects with preclinical Alzheimer’s disease

“…Comparable to GFAP, YKL-40 levels increase with age, in CSF, and also in plasma. When measured in plasma, higher plasma YKL-40 concentrations seem to be correlated with male sex, older age, APOE ε4 status, and cerebral accumulation of Aβ measured with PET [ 31 ]. Our sample did not find YKL-40 to be correlated with age, sex, APOE ε4 status and Aβ measured in CSF.…”

Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality

“…To date, no study has explicitly reported sex disaggregated data on the serum levels of YKL-40 in CKD or CVD populations. However, sex differences in plasma YKL-40 levels have been presented in studies assessing neuroinflammation conditions, such as Alzheimer's disease, where YKL-40 levels were found higher in males [59]. Whilst explicit sex differences in YKL-40 levels alone were not observed in our ESKD cohort, the sex-specific associations explored thereafter could give precedent to study YKL-40 further in a sex disaggregated approach including larger cohorts prospectively based on eGFR through CKD stages.…”