Detection and clinical significance of serum GGT and CTHRC1 expression levels in patients with Alzheimer's disease

doi:10.11958/20221105

Abstract

Abstract:

Objective To study the serum levels of gamma-glutamyl transferase (GGT) and collagen triple helix repeat containing 1 (CTHRC1) in Alzheimer's disease (AD) patients and their clinical significance. Methods A total of 120 AD patients diagnosed and treated in our hospital from January 2020 to January 2022 were selected as the AD group, and 60 healthy people who underwent physical examinations during the same period were selected as the control group. Enzyme-linked immunosorbent assay was used to detect serum expression levels of GGT, CTHRC1, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in each group. Serum hypersensitive C-reactive protein (hs-CRP) was detected by immunoturbidimetry. Pearson correlation analysis was used to analyze the correlation between serum GGT, CTHRC1, TNF-α, IL-1β, IL-6, CRP and Concise Mental State Scale (MMSE) score in the AD group. Multivariate Logistic regression analysis was used to analyze risk factors affecting the occurrence of AD. Receiver operating curve analysis was used to analyze the diagnostic value of serum GGT and CTHRC1 levels in the diagnosis of AD. Results The serum levels of GGT, CTHRC1, TNF-α, IL-6, IL-1β and hs-CRP were significantly higher in the AD group than those in the control group, and the MMSE score was significantly lower than that in the control group (P<0.05). The expression levels of serum GGT and CTHRC1 were positively correlated with levels of TNF-α, IL-6, IL-1β and hs-CRP in the AD group, and were negatively correlated with the MMSE score (P<0.05). Increased GGT and CTHRC1 levels and decreased MMSE score were independent risk factors for the occurrence of AD (P<0.05). The areas under the curve (95%CI) of serum GGT and CTHRC1 alone and in combination for the diagnosis of AD were 0.780 (0.726-0.836), 0.728 (0.705-0.810) and 0.909 (0.875-0.942), respectively. The diagnostic value of serum GGT and CTHRC1 combined detection for AD was significantly higher than that of serum GGT and CTHRC1 single index detection (Z=4.370, 5.657, P<0.05). Conclusion The serum expression levels of GGT and CTHRC1 are related to the inflammatory response and cognitive level in AD patients. The combined detection of both has high diagnostic value for AD.

Key words: Alzheimer disease, gamma-glutamyl transferase 1, early diagnosis, collagen triple helix repeat factor 1, inflammatory response

CLC Number:

R749.16

Figures/Tables 6

References 20

[1]	SCHELTENS P, DE STROOPER B, KIVIPELTO M, et al. Alzheimer's disease[J]. Lancet, 2021, 397(10284):1577-1590. doi:10.1016/S0140-6736(20)32205-4.
[2]	VEITCH D P, WEINER M W, AISEN P S, et al. Understanding disease progression and improving Alzheimer's disease clinical trials:Recent highlights from the Alzheimer's disease neuroimaging initiative[J]. Alzheimers Dement, 2019, 15(1):106-152. doi:10.1016/j.jalz.2018.08.005.
[3]	CORTI A, BELCASTRO E, DOMINICI S, et al. The dark side of gamma-glutamyltransferase (GGT):Pathogenic effects of an 'antioxidant' enzyme[J]. Free Radic Biol Med, 2020, 160(7):807-819. doi:10.1016/j.freeradbiomed.2020.09.005.
[4]	LEE Y B, HAN K, PARK S, et al. Gamma-glutamyl transferase variability and risk of dementia:A nationwide study[J]. Int J Geriatr Psychiatry, 2020, 35(10):1105-1114. doi:10.1002/gps.5332.
[5]	LI J, WANG Y, MA M, et al. Autocrine CTHRC1 activates hepatic stellate cells and promotes liver fibrosis by activating TGF-β signaling[J]. EBioMedicine, 2019, 40(7):43-55. doi:10.1016/j.ebiom.2019.01.009.
[6]	WANG H, DEY K K, CHEN P C, et al. Integrated analysis of ultra-deep proteomes in cortex,cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer's disease[J]. Mol Neurodegener, 2020, 15(1):43-49. doi:10.1186/s13024-020-00384-6.
[7]	周小炫, 谢敏, 陶静, 等. 简易智能精神状态检查量表的研究和应用[J]. 中国康复医学杂志, 2016, 31(6):694-696,706.
	ZHOU X X, XIE M, TAO J, et al. Research and application of the simple intelligent mental state examination scale[J]. Chinese Journal of Rehabilitation Medicine, 2016, 31(6):694-696,706. doi:10.3969/j.issn.1001-1242.2016.06.019.
[8]	BUTTERFIELD D A, HALLIWELL B. Oxidative stress,dysfunctional glucose metabolism and Alzheimer disease[J]. Nat Rev Neurosci, 2019, 20(3):148-160. doi:10.1038/s41583-019-0132-6.
[9]	ZHUANG X X, WANG S F, TAN Y, et al. Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson's disease models[J]. Cell Death Dis, 2020, 11(2):128-135. doi:10.1038/s41419-020-2322-6.
[10]	LEE D H, BLOMHOFF R, JACOBS D R J R. Is serum gamma glutamyltransferase a marker of oxidative stress?[J]. Free Radic Res, 2004, 38(6):535-539. doi:10.1080/10715760410001694026.
[11]	GASECKA A, SIWIK D, GAJEWSKA M, et al. Early biomarkers of neurodegenerative and neurovascular disorders in diabetes[J]. J Clin Med, 2020, 9(9):2807-2812. doi:10.3390/jcm9092807.
[12]	ZHANG W, TANG Z, SHI Y, et al. Association between gamma-glutamyl transferase,total bilirubin and systemic lupus erythematosus in chinese women[J]. Front Immunol, 2021, 12(29):6824-6830. doi:10.3389/fimmu.2021.682400.
[13]	谢淑玲, 伍文彬, 彭丽燕, 等. 脑铁超载相关蛋白与阿尔茨海默病相关性[J]. 中国老年学杂志, 2015, 35(12):3456-3459.
	XIE S L, WU W B, PENG L Y, et al. Correlation between brain iron overload-related proteins and Alzheimer's disease[J]. Chinese Journal of Gerontology, 2015, 35(12):3456-3459. doi:10.3969/j.issn.1005-9202.2015.12.132.
[14]	BATSIOS G, NAJAC C, CAO P, et al. In vivo detection of gamma-glutamyl-transferase up-regulation in glioma using hyperpolarized gamma-glutamyl-[1-(13)C]glycine[J]. Sci Rep, 2020, 10(1):6244-6250. doi:10.1038/s41598-020-63160-y.
[15]	KIM Y G, PARK G M, LEE S B, et al. Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics[J]. Sci Rep, 2020, 10(1):17994-17999. doi:10.1038/s41598-020-75078-6.
[16]	MEI D, ZHU Y, ZHANG L, et al. The role of CTHRC1 in regulation of multiple signaling and tumor progression and metastasis[J]. Mediators Inflamm, 2020, 2020(12):9578-9585. doi:10.1155/2020/9578701.
[17]	BAI B, WANG X, LI Y, et al. Deep multilayer brain proteomics identifies molecular networks in alzheimer's disease progression[J]. Neuron, 2020, 105(6):975-991. doi:10.1016/j.neuron.2019.12.015.
[18]	KIM J, KIM J, KIM D W, et al. Wnt5a induces endothelial inflammation via beta-catenin-independent signaling[J]. J Immunol, 2010, 185(2):1274-1282. doi:10.4049/jimmunol.1000181.
[19]	ZHENG M, ZHOU Q, LIU X, et al. CTHRC1 overexpression promotes cervical carcinoma progression by activating the Wnt/PCP signaling pathway[J]. Oncol Rep, 2019, 41(3):1531-1538. doi:10.3892/or.2019.6963.
[20]	MYNGBAY A, BEXEITOV Y, ADILBAYEVA A, et al. CTHRC1:A new candidate biomarker for improved rheumatoid arthritis diagnosis[J]. Front Immunol, 2019, 12(10):1353-1360. doi:10.3389/fimmu.2019.01353.

组别	n	TC	TG	HDL-C	LDL-C
对照组	60	3.93±0.41	1.42±0.31	0.98±0.15	2.73±0.36
AD组	120	4.05±0.46	1.46±0.30	1.01±0.17	2.81±0.38
t或χ²		1.709	0.834	1.159	1.355

组别	n	TC	TG	HDL-C	LDL-C
对照组	60	3.93±0.41	1.42±0.31	0.98±0.15	2.73±0.36
AD组	120	4.05±0.46	1.46±0.30	1.01±0.17	2.81±0.38
t或χ²		1.709	0.834	1.159	1.355

组别		n	GGT（U/L）		CTHRC1（μg/L）		TNF-α（ng/L）
对照组		60	23.87±6.09		32.73±5.64		147.35±13.12
AD组		120	47.14±7.92		43.27±6.42		196.27±12.42
t			19.985^＊＊		10.800^＊＊		24.446^＊＊
组别	IL-6 （ng/L）			IL-1β （ng/L）		hs-CRP （ng/L）		MMSE 评分（分）
对照组	61.34±11.54			28.29±6.28		1.91±0.73		28.34±1.04
AD组	106.34±13.27			38.34±7.14		5.08±0.62		15.66±3.22
t	22.370^＊＊			9.256^＊＊		30.446^＊＊		29.702^＊＊

组别		n	GGT（U/L）		CTHRC1（μg/L）		TNF-α（ng/L）
对照组		60	23.87±6.09		32.73±5.64		147.35±13.12
AD组		120	47.14±7.92		43.27±6.42		196.27±12.42
t			19.985^＊＊		10.800^＊＊		24.446^＊＊
组别	IL-6 （ng/L）			IL-1β （ng/L）		hs-CRP （ng/L）		MMSE 评分（分）
对照组	61.34±11.54			28.29±6.28		1.91±0.73		28.34±1.04
AD组	106.34±13.27			38.34±7.14		5.08±0.62		15.66±3.22
t	22.370^＊＊			9.256^＊＊		30.446^＊＊		29.702^＊＊

参数	GGT	CTHRC1
TNF-α	0.418^＊	0.474^＊
IL-6	0.435^＊	0.414^＊
IL-1β	0.514^＊	0.437^＊
hs-CRP	0.515^＊	0.638^＊
MMSE评分	-0.649^＊	-0.657^＊