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Soluble TREM2 and Alzheimer-related biomarker trajectories in the blood of patients with diabetes based on their cognitive status

  • Noriko Satoh-Asahara
    Correspondence
    Corresponding author at: Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, Japan.
    Affiliations
    Clinical Research Institute for Endocrine & Metabolic Disease, National Hospital Organization, Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan

    Department of Metabolic Syndrome and Nutritional Science, Research Institute of Environmental Medicine, Nagoya University, Aichi 464-8601, Japan
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  • Hajime Yamakage
    Affiliations
    Clinical Research Institute for Endocrine & Metabolic Disease, National Hospital Organization, Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan
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  • Masashi Tanaka
    Affiliations
    Clinical Research Institute for Endocrine & Metabolic Disease, National Hospital Organization, Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan

    Department of Physical Therapy, Health Science University, Yamanashi 401-0380, Japan
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  • Teruaki Kawasaki
    Affiliations
    Center of Neurological and Cerebrovascular Diseases, Koseikai Takeda Hospital, Kyoto, Japan
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  • Sayo Matsuura
    Affiliations
    Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba 263-0024, Japan
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  • Harutsugu Tatebe
    Affiliations
    Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba 263-0024, Japan
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  • Ichiro Akiguchi
    Affiliations
    Center of Neurological and Cerebrovascular Diseases, Koseikai Takeda Hospital, Kyoto, Japan
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  • Takahiko Tokuda
    Affiliations
    Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba 263-0024, Japan
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Published:October 19, 2022DOI:https://doi.org/10.1016/j.diabres.2022.110121

      Highlights

      • Decreased serum sTREM2 in diabetes-related dementia.
      • No decrease in the Aβ42/Aβ40 ratio in diabetes-related dementia.
      • Suggested involvement of a molecular cascade initiated by impaired microglial activation.
      • A new characteristic trajectory of blood biomarkers in diabetes-related dementia.

      Abstract

      Aim

      We aimed to elucidate the dynamics of blood biomarkers according to the severity of cognitive impairment in patients with type 2 diabetes mellitus (DM) and to identify useful biomarkers for diabetes-related dementia.

      Methods

      This was a cross-sectional, nested case-control study of 121 Japanese DM and non-DM patients with different levels of cognitive functioning. We evaluated participants’ cognitive functions, blood biomarkers related to Alzheimer’s disease, and soluble triggering receptors expressed on myeloid cells 2 (sTREM2). We then compared these biomarkers between the DM and non-DM and across the different cognitive strata.

      Results

      In all cognitive strata, significantly lower levels of serum sTREM2 were observed in the DM than in the non-DM. We also found that plasma levels of phosphorylated tau (p-tau) increased with increasing levels of cognitive decline in both the DM and non-DM. However, this was accompanied by a decrease in plasma amyloid-β(Aβ42/Aβ40 ratios in non-DM only.

      Conclusion

      This study revealed novel characteristic trajectories of dementia-related blood biomarkers in diabetes-related dementia, suggesting the pathological involvement of molecular cascades initiated by impaired microglial activation. This results in decreased serum sTREM2, followed by tauopathy without substantial amyloid plaques, reflected by plasma p-tau elevation with no decrease in the Aβ42/Aβ40 ratio.
      Clinical trials (the unique trial number and the name of the registry): UMIN000048032, https://www.umin.ac.jp.

      Keywords

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