Correlation between lymphocyte G-protein-coupled receptor kinase-5 level and cognitive impairment in patients with Alzheimer′s disease

doi:10.16150/j.1671-2870.2018.04.012

Abstract

Abstract: Objective: To investigate the correlation between G protein-coupled receptor kinase-5 (GRK5) level in peripheral lymphocytes and the degree of cognitive impairment in Alzheimer's disease(AD) patients. Methods: A total of 64 patients with AD during January 2015 to December 2017 were enrolled and divided into two groups, including 27 cases of mild dementia and 37 cases of moderate-to-severe dementia; 30 healthy subjects were served as controls. Enzyme-linked immunosorbent assay(ELISA) was used to detect the GRK5 level in peripheral lymphocytes of AD patients and controls. Results: The GRK5 level in mild and moderate-to-severe AD patients was significantly lower than that in controls (P<0.001). Moreover, the GRK5 level in moderate-to-severe AD patients was significantly lower than that in the mild AD patients (P<0.001). Linear regression analyses revealed a strong positive correlation between the GRK5 level and the Mini Mental State Examination (MMSE) score (P<0.001). Conclusions: Our data suggestes that low level of GRK5 is existed in AD patients and mirrored the impairment of cognitive state. GRK5 level of peripheral blood lymphocytes might be used as a novel biomarker for the early diagnosis of AD patients.

Key words: Alzheimer's disease, Cognitive impairment, G protein-coupled receptor kinase-5

CLC Number:

R741

SUN Jialan, HUANG Shu, LAI Xiaoyin, ZHU Wei, HU Rongguo, LI Longxuan. Correlation between lymphocyte G-protein-coupled receptor kinase-5 level and cognitive impairment in patients with Alzheimer′s disease[J]. Journal of Diagnostics Concepts & Practice, 2018, 17(04): 419-422.

References

[1] 赵仲艳, 何祥英, 吴婵姬, 等. GRK5功能缺失与阿尔茨海默病的相关性研究进展[J]. 海南医学,2015,26(1):82-85.
[2] Suo Z, Wu M, Citron BA, et al.Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimer's disease: an association with early beta-amyloid accumulation[J]. J Neurosci,2004,24(13):3444-3452.
[3] Suo WZ, Li L.Dysfunction of G protein-coupled receptor kinases in Alzheimer's disease[J]. Scientific World Journal,2010,10:1667-1678.
[4] American Psychiatric Association.Mood disorders. Diagnostic and statistical manual of mental disorders(Fourth edition. DSM-IV)[M]. Washington DC:American Psychiatric Association,1994:317-391.
[5] Rait G, Fletcher A, Smeeth L, et al.Prevalence of cognitive impairment: results from the MRC trial of assessment and management of older people in the community[J]. Age Ageing,2005,34(3):242-248.
[6] Nybo H, Petersen HC, Gaist D, et al.Predictors of mortality in 2,249 nonagenarians--the Danish 1905-Cohort Survey[J]. J Am Geriatr Soc,2003,51(10):1365-1373.
[7] Bassuk SS, Wypij D, Berkman LF.Cognitive impairment and mortality in the community-dwelling elderly[J]. Am J Epidemiol,2000,151(7):676-688.
[8] Suo Z, Wu M, Citron BA, et al.Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimer's disease: an association with early beta-amyloid accumulation[J]. J Neurosci,2004,24(13):3444-3452.
[9] Liu J, Rasul I, Sun Y, et al.GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization[J]. J Biol Chem,2009,284(29):19564-19571.
[10] Suo Z, Cox AA, Bartelli N, et al.GRK5 deficiency leads to early Alzheimer-like pathology and working memory impairment[J]. Neurobiol Aging,2007,28(12):1873-1888.
[11] Li L, Liu J, Suo WZ.GRK5 deficiency exaggerates inflammatory changes in TgAPPsw mice[J]. J Neuroinflammation,2008,5:24.
[12] Cheng S, Li L, He S, et al.GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity[J]. J Biol Chem,2010,285(53):41541-41548.
[13] He M, Singh P, Cheng S, et al.GRK5 Deficiency leads to selective basal forebrain cholinergic neuronal vulnerability[J]. Sci Rep,2016,6:26116.
[14] Saitoh T, Horsburgh K, Masliah E.Hyperactivation of signal transduction systems in Alzheimer's disease[J]. Ann N Y Acad Sci,1993,695:34-41.
[15] Fowler CJ, Garlind A, O'Neill C, et al. Receptor-effector coupling dysfunctions in Alzheimer's disease[J]. Ann N Y Acad Sci,1996,786:294-304.
[16] Leosco D, Fortunato F, Rengo G, et al.Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease[J]. Neurosci Lett,2007, 415(3):279-282.