Association of Folate Metabolites and Mitochondrial Function in Peripheral Blood Cells in Alzheimer’s Disease: A Matched Case-Control Study

Article type: Research Article

Authors: Lv, Xin^{a; b} | Zhou, Dongtao^{a; b} | Ge, Baojin^{a; b} | Chen, Hui^c | Du, Yue^d | Liu, Shuai^e | Ji, Yong^e | Sun, Changqing^f | Wang, Guangshun^g | Gao, Yuxia^h | Li, Wen^{a; b; *} | Huang, Guowei^{a; b; *}

Affiliations: [a] Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China | [b] Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China | [c] School of Nursing, Tianjin Medical University, Tianjin, China | [d] Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China | [e] Department of Neurology, and Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China | [f] Neurosurgical Department of Baodi Clinical College of Tianjin Medical University, Tianjin, China | [g] Department of Tumor, Baodi Clinical College of Tianjin Medical University, Tianjin, China | [h] Department of Cardiology, General Hospital of Tianjin Medical University, Tianjin, China

Correspondence: [*] Correspondence to: Dr. Guowei Huang, Professor and Dr. Wen Li, Associate Professor, Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. Tel./Fax: +86 22 83336603; E-mails: [email protected] and [email protected].

Abstract: Background:The nutrition state plays an important role in the progress of aging. Folate may play a role in protecting mitochondrial (mt) DNA by reducing oxidative stress. Objective:The primary aim of this study was to examine the association of mitochondrial oxidative damage with risk of Alzheimer’s disease (AD), and to explore the possible role of folate metabolites in this association in a matched case-control study. Methods:Serum folate metabolites and mitochondrial function in peripheral blood cells were determined in 82 AD cases and 82 healthy controls, individually matched by age, gender, and education. Results:AD patients had lower serum levels of folate and higher homocysteine (Hcy) concentration. AD patients had a reduced mtDNA copy number, higher mtDNA deletions, and increased 8-OHdG content in mtDNA indicative of reduced mitochondrial function. The highest level of mtDNA copy number would decrease the risk of AD (OR = 0.157, 95% CI: 0.058–0.422) compared to the lowest level, independently of serum folate, and Hcy levels. Serum folate levels correlated with low 8-OHdG content in mtDNA both in AD patients and controls, independently of serum Hcy level. Moreover, serum Hcy levels correlated with low copy number in mtDNA both in AD patients and controls, independently of serum folate levels. Conclusion:In conclusion, mitochondrial function in peripheral blood cells could be associated with risk of AD independent of multiple covariates. AD patients with a folate deficiency or hyperhomocysteinemia had low mitochondrial function in peripheral blood cells. However, further randomized controlled trials are need to determine a causal effect.

Keywords: Alzheimer’s disease, China, folate metabolites, mitochondrial function, peripheral blood cells

DOI: 10.3233/JAD-190477

Journal: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1133-1142, 2019