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• Clinical Article •
Associations between plasma chitinase-3-like protein 1 levels and white matter microstructure in patients with amnestic mild cognitive impairment: A DTI study
XU Qu  LUO Xiaomei  WU Wenlan  ZHANG Junzhu  XU Qiufeng  ZHANG Mengdi  HE Qingxia  CAI Ming  MA Qiang 

DOI:10.12015/issn.1674-8034.2026.02.007.


[Abstract] Objective To investigate alterations in plasma chitinase-3-like protein 1 (CHI3L1, also known as YKL-40) levels in patients with amnestic mild cognitive impairment (aMCI) and their association with white matter microstructural damage.Materials and Methods Thirty patients with aMCI and 20 cognitively unimpaired (CU) controls were recruited. All participants underwent cognitive assessments, plasma YKL-40 quantification, and diffusion tensor imaging (DTI). A region-of-interest (ROI) - based analysis was performed to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) across selected white matter regions. Between-group differences in plasma YKL-40 levels were assessed. Partial correlation and multiple linear regression analyses were conducted to examine associations between plasma YKL-40 levels and DTI parameters, and to determine their independent predictive effects.Results Plasma YKL-40 levels were significantly higher in the aMCI group than in the CU group (F = 4.131, P = 0.048). Compared with CU, the aMCI group showed significantly decreased FA in the body of the fornix (F = 4.295, P = 0.044) and increased MD (F = 4.933, P = 0.031), AD (F = 4.482, P = 0.040), and RD (F = 4.988, P = 0.030). Plasma YKL-40 levels were positively correlated with left cingulate MD (r = 0.392, P = 0.006), left cingulate RD (r = 0.329, P = 0.022), and right cingulate RD (r = 0.347, P = 0.016). Multiple regression analyses indicated that, after adjusting for age, sex, education, and group status, plasma YKL-40 remained independently associated with left cingulate MD (β = 0.404, P = 0.015), left cingulate RD (β = 0.341, P = 0.038), and right cingulate RD (β = 0.372, P = 0.023).Conclusions Plasma YKL-40 levels are elevated in patients with aMCI and are closely linked to the degree of white matter microstructural disruption in the cingulate gyrus. These findings suggest that peripheral YKL-40 may serve as a potential biomarker reflecting early neuroinflammatory activity and white matter degeneration in the prodromal stage of Alzheimer's disease.
[Keywords] amnestic mild cognitive impairment；diffusion tensor imaging；magnetic resonance imaging；white matter microstructure；chitinase-3-like protein 1；plasma biomarker

XU Qu1   LUO Xiaomei2   WU Wenlan3   ZHANG Junzhu1   XU Qiufeng1   ZHANG Mengdi1   HE Qingxia1   CAI Ming1   MA Qiang1*  

1 Department of Neurology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China

2 Department of Geriatrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

3 Department of Neurology, China Resources Wuhan General Hospital, Wuhan 430080, China

Corresponding author: MA Q, E-mail: maqiang@dlu.edu.cn

Conflicts of interest   None.

Received  2025-10-27
Accepted  2026-01-08
DOI: 10.12015/issn.1674-8034.2026.02.007
DOI:10.12015/issn.1674-8034.2026.02.007.

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