Journal of Diagnostics Concepts & Practice >

2026 , Vol. 25 >Issue 02: 174 - 182

DOI: https://doi.org/10.16150/j.1671-2870.2026.02.008

Original articles

The effect of KL-VS gene on medial temporal lobe volume in patients with mild cognitive impairment： A study based on MRI

  • LIU Xiaocao ,
  • ZENG Qingze ,
  • LI Yixia ,
  • LI Kaicheng ,
  • LUO Xiao ,
  • YAN Shaozhen ,
  • LU Jie
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  • 1 Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
    2 Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing 100053, China
    3 Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, China
    4 The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China

Received date: 2025-10-27

  Revised date: 2026-01-04

  Accepted date: 2026-01-05

  Online published: 2026-04-25

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Abstract

Objective Based on magnetic resonance imaging (MRI), this study aims to explore the impact of the KL-VS functional haplotype heterozygous gene (KL-VShet+) in the Klotho gene on the subregion structure of the medial temporal lobe,which presents abnormal in the brain region in the earliest progression of Alzheimer's disease (AD), as well as its relationship with the decline in cognitive function associated with AD pathology. Methods A total of 48 participants from the AD Neuroimaging Initiative database (with genome-wide association analysis data and high-resolution magnetic resonance ima-ging data from October 2018 to June 2024) were enrolled, comprising 16 KL-VShet+ carriers [8 cognitively normal, CN; 8 amnestic mild cognitive impairment (MCI), aMCI] and 32 non-carriers (KL-VShet-) (16 CN and 16 aMCI). Structural MRI data were analyzed using automatic segmentation of hippocampal subfields to calculate medial temporal lobe subregion volumes. Group differences in medial temporal lobe subregion volume, cognitive function, and pathological proteins (amyloid β- protein, Aβ/tau protein) were compared using analysis of variance. Moderation analysis was conducted with SPSS 27 (PROCESS v4.1). Results Significant differences were observed between KL-VShet+ and KL-VShet- individuals in medial temporal lobe subregion volumes, cognitive function, and pathological protein (Aβ/tau) burden (P<0.05). In the MCI group, KL-VShet+ carriers showed significantly larger volumes in the left hippocampal subfield cornu ammonis 3 (CA3) (79.80±29.75 mm3) and dentate gyrus (755.19±186.68 mm3) compared to KL-VShet- individuals (52.46±15.53 mm3, 710.09±146.09 mm3) (P<0.05). Tau protein deposition was significantly lower in KL-VShet+ individuals than in KL-VShet- individuals (P<0.05), and Aβ deposition showed a lower trend, although the difference did not reach statistical significance (P=0.054). Moderation analysis showed that, among KL-VShet+ individuals, the volumes of multiple medial temporal lobe subregions had significant positive moderating effects on the relationship between AD-related pathology and cognitive performance, mainly reflected in memory scores. The volume of the left CA3 subregion significantly moderated the relationship between Aβ deposition and memory function scores, while the volumes of multiple bilateral medial temporal lobe subregions significantly moderated the relationship between tau deposition and memory scores (interaction term β ranged from 0.000 5 to 0.074 5, and the 95% confidence interval ranged from -0.002 0 to 0.172 3, P<0.05). Conclusions The KL-VShet+ gene product may exert a neuroprotective effect by slowing down the volume atrophy of medial temporal lobe regions, such as the hippocampus, thereby mitigating the damage to cognitive function caused by pathological protein deposition in patients with mild cognitive impairment (MCI). KL-VShet may serve as a novel therapeutic target for Alzheimer's disease (AD).

Key words： Alzheimer's disease; Mild cognitive impairment; Magnetic resonance imaging; Medial temporal lobe subregions; Klotho gene

Cite this article

LIU Xiaocao , ZENG Qingze , LI Yixia , LI Kaicheng , LUO Xiao , YAN Shaozhen , LU Jie . The effect of KL-VS gene on medial temporal lobe volume in patients with mild cognitive impairment： A study based on MRI[J]. Journal of Diagnostics Concepts & Practice, 2026 , 25(02) : 174 -182 . DOI: 10.16150/j.1671-2870.2026.02.008

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