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Plasma Clusterin as a Potential Link Between Diabetes and Alzheimer Disease

Authors
 Junghee Ha  ;  Min Kyong Moon  ;  Hyunjeong Kim  ;  Minsun Park  ;  So Yeon Cho  ;  Jimin Lee  ;  Jun-Young Lee  ;  Eosu Kim 
Citation
 JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.105(9) : dgaa378, 2020-09 
Journal Title
 JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 
ISSN
 0021-972X 
Issue Date
2020-09
Keywords
Alzheimer disease ; biomarker ; brain atrophy ; clusterin ; diabetes mellitus ; insulin resistance
Abstract
Objective: Plasma clusterin, a promising biomarker of Alzheimer disease (AD), has been associated with diabetes mellitus (DM). However, clusterin has not been investigated considering a relationship with both DM and AD. In this study, we aimed to investigate the individual and interactive relationships of plasma clusterin levels with both diseases. Design: Cross-sectional observation study. Methods: We classified participants by the severity of cognitive (normal cognition, mild cognitive impairment [MCI], and AD) and metabolic (healthy control, prediabetes, and DM) impairments. We evaluated the cognitive and metabolic functions of the participants with neuropsychological assessments, brain magnetic resonance imaging, and various blood tests, to explore potential relationships with clusterin. Results: Plasma clusterin levels were higher in participants with AD and metabolic impairment (prediabetes and DM). A two-way ANCOVA revealed no synergistic, but an additive effect of AD and DM on clusterin. Clusterin was negatively correlated with cognitive scores. It was also associated with metabolic status indicated by glycated hemoglobin A1c (HbA1c), the Homeostatic Model Assessment for Insulin Resistance index, and fasting C-peptide. It showed correlations between medial temporal atrophy and periventricular white matter lesions, indicating neurodegeneration and microvascular insufficiency, respectively. Further mediation analysis to understand the triadic relationship between clusterin, AD, and DM revealed that the association between DM and AD was significant when clusterin is considered as a mediator of their relationship. Conclusions: Clusterin is a promising biomarker of DM as well as of AD. Additionally, our data suggest that clusterin may have a role in linking DM with AD as a potential mediator.
Full Text
https://academic.oup.com/jcem/article/105/9/3058/5860166
DOI
10.1210/clinem/dgaa378
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Ha, Junghee(하정희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179978
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