The serum expression level and clinical significance of Apelin13 and FKBP5 in patients with Alzheimer's disease

doi:10.11958/20220022

Abstract

Abstract:

Objective To investigate the serum expression level and clinical significance of Apelin13 and FK506 binding protein 51 (FKBP5) in patients with Alzheimer's disease (AD). Methods A total of 93 AD patients were selected (the AD group), and 90 healthy subjects of the same age for physical examination were selected as the control group. The serum levels of Apelin13 and FKBP5 mRNA were compared between the groups. The correlation between Apelin13, FKBP5 mRNA and Mini-mental State Examination (MMSE) score was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Apelin13 and FKBP5 mRNA for severe cognitive impairment in AD patients. Results The serum level of Apelin13 and MMSE scores were significantly lower in the AD group than those in the control group, while the level of FKBP5 mRNA was significantly higher in the AD group than that in the control group (P<0.01). The serum levels of Apelin13 decreased sequentially in patients with mild, moderate and severe AD, while levels of FKBP5 mRNA increased sequentially (all P<0.05). Binary Logistic regression analysis showed that higher MMSE score and Apelin13 were protective factors for AD, while higher FKBP5 mRNA was a risk factor for the development of AD (all P<0.05). MMSE score was negatively correlated with the serum level of FKBP5 mRNA and positively correlated with the level of Apelin13 in AD patients (all P<0.05). ROC curve showed that the AUC value [0.884 (0.808-0.961)] of Apelin13 combined with FKBP5 mRNA was significantly higher than that of Apelin13 or FKBP5 mRNA [0.776 (0.673-0.879) or 0.801 (0.699-0.902)], and the sensitivity and specificity of combined diagnosis were 81.25 and 86.89, respectively (all P<0.05). Conclusion The serum level of Apelin13 is decreased in AD patients, while FKBP5 mRNA is increased. Apelin13 combined with FKBP5 mRNA has good diagnostic efficacy for severe cognitive impairment in AD patients.

Key words: Alzheimer disease, cognition disorders, Tacrolimus binding proteins, ROC curve, early diagnosis, Apelin13, FK506 binding protein 51

CLC Number:

R742

Figures/Tables 5

References 16

[1]	TEZEL G, TIMUR S S, BOZKURT I, et al. A Snapshot on the current status of Alzheimer's disease,treatment perspectives,in-vitro and in-vivo research studies and future opportunities[J]. Chem Pharm Bull(Tokyo), 2019, 67(10):1030-1041.doi: 10.1248/cpb.c19-00511.
[2]	VURAL E, HAZAR L, KARAKUKCU C, et al. Apelin-13:A promising biomarker for age-related macular degeneration?[J]. Ophthalmologica, 2021, 244(2):102-109. doi: 10.1159/000513050.
[3]	FULLER K, GRAVLEE C C, MCCARTY C, et al. Stressful social environment and financial strain drive depressive symptoms,and reveal the effects of a FKBP5 variant and male sex,in African Americans living in Tallahassee[J]. Am J Phys Anthropol, 2021, 176(4):572-583. doi: 10.1002/ajpa.24362.
[4]	LOBUONO V, BONANNO I, CORALLO F, et al. Qualitative analysis of minimental state examination Pentagon in vascular dementia and Alzheimer's disease:a longitudinal explorative study[J]. J Stroke Cerebrovasc Dis, 2018, 27(6):1666-1672. doi: 10.1016/j.jstrokecerebrovasdis.2018.01.021.
[5]	PADMANNBHAN P, KNEYNSBERG A, GOTZ J, et al. Super-resolution microscopy:A closer look at synaptic dysfunction in Alzheimer disease[J]. Nat Rev Neurosci, 2021, 22(12):723-740. doi: 10.1038/s41583-021-00531-y.
[6]	陈紫晗, 孙琳琳, 张艺璇, 等. β-淀粉样蛋白清除障碍在阿尔兹海默症发病中的作用[J]. 生理科学进展, 2019, 50(2):149-152.
	CHEN Z H, SUN L L, ZHANG Y X, et al. The roles of amyloid β-protein clearance impairment in the Alzheimer's disease[J]. Progress in Physiological Sciences, 2019, 50(2):149-152. doi: 10.3969/j.issn.0559-7765.2019.02.016.
[7]	ANGELOPOULUO E, PAUDEL Y N, BOUGEA A, et al. Impact of the apelin/APJ axis in the pathogenesis of Parkinson's disease with therapeutic potential[J]. J Neurosci Res, 2021, 99(9):2117-2133. doi: 10.1002/jnr.24895.
[8]	WANG X, TIAN X, PEI L L, et al. The association between serum apelin-13 and the prognosis of acute ischemic stroke[J]. Transl Stroke Res, 2020, 11(4):700-707. doi: 10.1007/s12975-019-00769-w.
[9]	SHAO Z Q, DOU S S, ZHU J G, et al. Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury[J]. Neural Regen Res, 2021, 16(6):1044-1051. doi: 10.4103/1673-5374.300725.
[10]	LIU W, NIU F, SHA H, et al. Apelin-13/APJ system delays intervertebral disc degeneration by activating the PI3K/AKT signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2020, 24(6):2820-2828. doi: 10.26355/eurrev_202003_20643.
[11]	WILLI R A, FALTERMANN S, HETTICH T, et al. Active glucocorticoids have a range of important adverse developmental and physiological effects on developing Zebrafish Embryos[J]. Environ Sci Technol, 2018, 52(2):877-885. doi: 10.1021/acs.est.7b06057.
[12]	RICHTER A, AL-BAYATI M, PARASKEVOPOULOU F, et al. Interaction of FKBP5 variant rs3800373 and city living alters the neural stress response in the anterior cingulate cortex[J]. Stress, 2021, 24(4):421-429. doi: 10.1080/10253890.2020.1855420.
[13]	SABBAGH J J, CORDOVA R A, ZHENG D, et al. Targeting the FKBP51/GR/Hsp90 complex to identify functionally relevant treatments for depression and PTSD[J]. ACS Chem Biol, 2018, 13(8):2288-2299. doi: 10.1021/acschembio.8b00454.
[14]	KE X R, FU Q, MAJNIK A, et al. Adverse early life environment induces anxiety-like behavior and increases expression of FKBP5 mRNA splice variants in mouse brain[J]. Physiol Genomics, 2018, 50(11):973-981. doi: 10.1152/physiolgenomics.00054.2018.
[15]	YANG S S, LI H, TANG L, et al. Apelin-13 protects the heart against ischemia-reperfusion injury through the RISK-GSK-3β-mPTP pathway[J]. Arch Med Sci, 2015, 11(5):1065-1073. doi: 10.5114/aoms.2015.54863.
[16]	AMINYAVARI S, ZAHMATKESH M, KHODAGHOLI F, et al. Anxiolytic impact of Apelin-13 in a rat model of Alzheimer's disease:Involvement of glucocorticoid receptor and FKBP5[J]. Peptides, 2019, 18(3):170102-170110. doi: 10.1016/j.peptides.2019.170102.

组别	n	LDL-C （mmol/L）	TC （mmol/L）	Apelin13 （μg/L）	FKBP5 mRNA	MMSE 评分（分）
对照组	90	2.03±0.59	3.78±1.06	43.69±10.06	1.13±0.32	28.29±1.68
AD组	93	2.18±0.63	4.04±1.17	17.82±5.07	3.88±1.11	15.21±4.61
t		1.661	1.574	21.857^＊＊	22.928^＊＊	25.336^＊＊

组别	n	LDL-C （mmol/L）	TC （mmol/L）	Apelin13 （μg/L）	FKBP5 mRNA	MMSE 评分（分）
对照组	90	2.03±0.59	3.78±1.06	43.69±10.06	1.13±0.32	28.29±1.68
AD组	93	2.18±0.63	4.04±1.17	17.82±5.07	3.88±1.11	15.21±4.61
t		1.661	1.574	21.857^＊＊	22.928^＊＊	25.336^＊＊

因素	B	SE	Wald χ²	P	OR（95%CI）
MMSE评分	-0.341	0.142	5.751	0.016	0.711（0.538~0.940）
FKBP5 mRNA	0.791	0.227	12.121	<0.001	2.206（1.413~3.444）
Apelin13	-0.794	0.268	8.802	0.003	0.452（0.267~0.764）
常数项	-0.687	0.263	6.823	<0.001	0.503

因素	B	SE	Wald χ²	P	OR（95%CI）
MMSE评分	-0.341	0.142	5.751	0.016	0.711（0.538~0.940）
FKBP5 mRNA	0.791	0.227	12.121	<0.001	2.206（1.413~3.444）
Apelin13	-0.794	0.268	8.802	0.003	0.452（0.267~0.764）
常数项	-0.687	0.263	6.823	<0.001	0.503

类型	n	Apelin13（μg/L）	FKBP5 mRNA
轻度组	10	25.62±6.91	3.09±0.72
中度组	51	18.92±5.03^a	3.72±0.91^a
重度组	32	13.63±3.27^ab	4.38±0.96^ab
F		27.359^＊＊	9.373^＊＊