The Relationship Between Plasma DPP4 Activity to BDNF Ratio and Mild Cognitive Impairment in Elderly Population With Normal Glucose Tolerance

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2019 Mar 20

PMID 30886577

Citations 4

Authors

Liuping Xiao

Bo Ge

Xu Chen

Bo Chen

Linyuan Qin

Xueping Hu

Haidong Pan

Yujie Chen

Li Tian

Yun Gao

Tianpeng Zheng

Affiliations

Soon will be listed here.

Abstract

Since decreased brain-derived neurotrophic factor (BDNF) and increased dipeptidyl peptidase-4 (DPP4) activity have both been implicated in the pathogenesis of mild cognitive impairment (MCI), the aim of our study was to evaluate the association of MCI with plasma DPP4 activity to BDNF ratio (DBR) in an elderly population with normal glucose tolerance. We cross-sectionally measured C-reactive protein, interleukin-6, nitrotyrosine, 8-iso-PGF2a, DPP4 activity BDNF and calculated the DBR in a total of 1,066 elderly participants in China. MCI was determined by the Montreal Cognitive Assessment and finally confirmed by neurologists. An inverse correlation was found between DPP4 activity and BDNF ( = -0.456, < 0.001) and this inverse correlation was partly mediated by nitrotyrosine and 8-iso-PGF2a. Across rising quartiles of DBR, nitrotyrosine, 8-iso-PGF2a, C-reactive protein and interleukin-6 progressively increased, whereas the Montreal Cognitive Assessment score progressively decreased. Subjects in the lowest quartile of BDNF and highest quartiles of DBR and DPP4 activity, had higher MCI risk compared with subjects in the highest quartile of the BDNF and lowest quartiles of DBR and DPP4 activity, respectively (all < 0.05). The odds ratio for MCI became more pronounced with decreased BDNF and increased DPP4. In conclusion, a negative correlation was found between DPP4 activity and BDNF, and this negative correlation was partly mediated by oxidative stress, not inflammation. The DBR was positively associated with MCI and thus may be used as a novel risk biomarker for MCI in an elderly population with normal glucose tolerance.

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References

Durinx C, Neels H, Van der Auwera J, Naelaerts K, Scharpe S, De Meester I . Reference values for plasma dipeptidyl-peptidase IV activity and their association with other laboratory parameters. Clin Chem Lab Med. 2001; 39(2):155-9. DOI: 10.1515/CCLM.2001.026. View

Huang E, Reichardt L . Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001; 24:677-736. PMC: 2758233. DOI: 10.1146/annurev.neuro.24.1.677. View

Weaver J, Huang M, Albert M, Harris T, Rowe J, Seeman T . Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology. 2002; 59(3):371-8. DOI: 10.1212/wnl.59.3.371. View

Wu A, Ying Z, Gomez-Pinilla F . The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci. 2004; 19(7):1699-707. DOI: 10.1111/j.1460-9568.2004.03246.x. View

Nasreddine Z, Phillips N, Bedirian V, Charbonneau S, Whitehead V, Collin I . The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4):695-9. DOI: 10.1111/j.1532-5415.2005.53221.x. View

Kuo H, Yen C, Chang C, Kuo C, Chen J, Sorond F . Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol. 2005; 4(6):371-80. DOI: 10.1016/S1474-4422(05)70099-5. View

Krabbe K, Nielsen A, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C . Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2006; 50(2):431-8. DOI: 10.1007/s00125-006-0537-4. View

Luchsinger J, Reitz C, Patel B, Tang M, Manly J, Mayeux R . Relation of diabetes to mild cognitive impairment. Arch Neurol. 2007; 64(4):570-5. DOI: 10.1001/archneur.64.4.570. View

Trajkovska V, Marcussen A, Vinberg M, Hartvig P, Aznar S, Knudsen G . Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull. 2007; 73(1-3):143-9. DOI: 10.1016/j.brainresbull.2007.03.009. View

10.

Marioni R, Strachan M, Reynolds R, Lowe G, Mitchell R, Fowkes F . Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes. 2009; 59(3):710-3. PMC: 2828661. DOI: 10.2337/db09-1163. View

11.

Petersen R, Roberts R, Knopman D, Boeve B, Geda Y, Ivnik R . Mild cognitive impairment: ten years later. Arch Neurol. 2009; 66(12):1447-55. PMC: 3081688. DOI: 10.1001/archneurol.2009.266. View

12.

Tian L, Gao J, Hao J, Zhang Y, Yi H, OBrien T . Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor. Endocrinology. 2010; 151(7):3049-60. DOI: 10.1210/en.2010-0068. View

13.

Ceriello A, Esposito K, Testa R, Bonfigli A, Marra M, Giugliano D . The possible protective role of glucagon-like peptide 1 on endothelium during the meal and evidence for an "endothelial resistance" to glucagon-like peptide 1 in diabetes. Diabetes Care. 2011; 34(3):697-702. PMC: 3041210. DOI: 10.2337/dc10-1949. View

14.

Ooi C, Loke S, Yassin Z, Hamid T . Carbohydrates for improving the cognitive performance of independent-living older adults with normal cognition or mild cognitive impairment. Cochrane Database Syst Rev. 2011; (4):CD007220. PMC: 7388979. DOI: 10.1002/14651858.CD007220.pub2. View

15.

Albert M, DeKosky S, Dickson D, Dubois B, Feldman H, Fox N . The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):270-9. PMC: 3312027. DOI: 10.1016/j.jalz.2011.03.008. View

16.

Shah Z, Kampfrath T, Deiuliis J, Zhong J, Pineda C, Ying Z . Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation. 2011; 124(21):2338-49. PMC: 4224594. DOI: 10.1161/CIRCULATIONAHA.111.041418. View

17.

Zhong J, Rao X, Deiuliis J, Braunstein Z, Narula V, Hazey J . A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-induced visceral inflammation. Diabetes. 2012; 62(1):149-57. PMC: 3526020. DOI: 10.2337/db12-0230. View

18.

Molendijk M, Spinhoven P, Polak M, Bus B, Penninx B, Elzinga B . Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484). Mol Psychiatry. 2013; 19(7):791-800. DOI: 10.1038/mp.2013.105. View

19.

Ishibashi Y, Matsui T, Maeda S, Higashimoto Y, Yamagishi S . Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor. Cardiovasc Diabetol. 2013; 12:125. PMC: 3765742. DOI: 10.1186/1475-2840-12-125. View

20.

Ceriello A, Novials A, Ortega E, Canivell S, La Sala L, Pujadas G . Vitamin C further improves the protective effect of glucagon-like peptide-1 on acute hypoglycemia-induced oxidative stress, inflammation, and endothelial dysfunction in type 1 diabetes. Diabetes Care. 2013; 36(12):4104-8. PMC: 3836129. DOI: 10.2337/dc13-0750. View