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. 2025 May 12:16:1516975.
doi: 10.3389/fimmu.2025.1516975. eCollection 2025.

Heat shock protein 90α may serve as a biomarker for mild cognitive impairment in type 2 diabetes mellitus patients without diabetic nephropathy

Hui Zhang #  1 , Meiyan Chi #  2   3 , Songtao Feng #  4 , Wenwen Zhu  5 , Hongxiao Wang  6 , Wan Zhou  3 , Bing Song  6 , Wei Wang  2   3 , Haoqiang Zhang  3
Affiliations

Heat shock protein 90α may serve as a biomarker for mild cognitive impairment in type 2 diabetes mellitus patients without diabetic nephropathy

Hui Zhang et al. Front Immunol. .

Abstract

Aim: Chronic inflammation associated oxidative stress is a key factor in complications of type 2 diabetes mellitus (T2DM), including mild cognitive impairment (MCI), partly associated with cerebrovascular lesions including both macrovascular and microvascular changes, and diabetic nephropathy (DN), a kind of diabetic microvascular complication. Heat shock protein 90α (Hsp90α) is known to play a significant role in inflammation associated oxidative stress and DN. This study aims to explore the role of Hsp90α in MCI and its potential as a diagnostic marker for MCI in T2DM patients.

Methods: We included 119 T2DM patients and analyzed their clinical data, Hsp90α levels, and cognitive scores. The relationships among Hsp90α, cognitive function, and urinary albumin-to-creatinine ratio (UACR) were also examined. Binary logistic regression was used to identify MCI risk factors, and ROC curves assessed Hsp90α's diagnostic value for MCI in patients, with or without DN.

Results: Patients with MCI exhibit worse cognitive function, higher UACR, and elevated Hsp90α levels compared to those without MCI. Increased Hsp90α was linked to lower cognitive scores and was identified as a risk factor for MCI. Patients with DN had a higher rate of MCI and cognitive decline than those without DN, and Hsp90α levels correlated with UACR, a DN marker. In patients without DN, higher Hsp90α was a risk factor for MCI; however, this was not observed in those with DN. An Hsp90α cut-off point of 69.105 ng/mL had a sensitivity of 60.0% and specificity of 91.4% for predicting MCI in patients without DN.

Conclusions: Elevated Hsp90α level is a risk factor for cognitive impairment and may serve as a biomarker for MCI in T2DM patients without DN.

Keywords: diabetic nephropathy; heat shock protein 90α; inflammation; mild cognitive impairment; oxidative stress; type 2 diabetes mellitus.

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Conflict of interest statement

All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ROC curve of Hsp90α for the sensitivity and specificity of MCI in patients with T2DM. The area under the curve is 0.656 in all patients (A). Additionally, the area under the curve is 0.597 and 0.781 in patients with and without DN, respectively (B). It is determined that the diagnostic cut-off value for Hsp90α to be 69.105 pg/ml, revealed a sensitivity of 60.0% and specificity of 91.4% in T2DM patients without DN (Youden’s index=0.514). ROC, Receiver operating characteristic; Hsp90α, Heat shock protein 90α; MCI, mild cognitive impairment; T2DM, type 2 diabetes mellitus; DN, diabetic nephropathy; Hsp90α, Heat shock protein 90α.
See this image and copyright information in PMC

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