Elevated Plasma Angiogenesis Factors in Alzheimer's Disease

Article type: Research Article

Authors: Qin, Wei^{a; b; c; d} | Jia, Xiangfei^e | Wang, Fen^{a; b; c; d} | Zuo, Xiumei^{a; b; c; d} | Wu, Liyong^{a; b; c; d} | Zhou, Aihong^{a; b; c; d} | Li, Dan^{a; b; c; d} | Min, Baoquan^{a; b; c; d} | Wei, Cuibai^{a; b; c; d} | Tang, Yi^{a; b; c; d} | Xing, Yi^{a; b; c; d} | Dong, Xiumin^{a; b; c; d} | Wang, Qi^{a; b; c; d} | Gao, Yining^{a; b; c; d} | Li, Ying^{a; b; c; d} | Jia, Jianping^{a; b; c; d; *}

Affiliations: [a] Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China | [b] Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China | [c] Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China | [d] Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China | [e] Department of Computer Science, University of Otago, Dunedin, New Zealand

Correspondence: [*] Correspondence to: Jianping Jia, MD, PhD, Department of Neurology, Xuan Wu Hospital of the Capital Medical University, 45 Changchun Street, Beijing 100053, China. Tel.: +86 10 8319 8730; Fax: +86 10 8317 1070; E-mail: jjp@ccmu.edu.cn; jiajp@vip.126.com.

Abstract: Evidence has shown that aberrant angiogenesis is an integral part of Alzheimer's disease (AD). Angiogenesis is a complex process requiring successive activation of a rather large series of factors. The aim of this study was to determine which angiogenesis molecule(s) abnormalities were changed in plasma of AD subjects and whether plasma levels of angiogenesis factors were associated with cognitive function and risk of AD. Discovery-phase antibody arrays were used to detect plasma concentrations of 55 angiogenesis-related factors. Enzyme-linked immunosorbent assays (ELISAs) in a large cohort were further performed to identify the association of plasma angiogenesis factors with AD. We found that plasma angiogenin (ANG) and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) levels were higher in patients with AD than those in normal subjects. Significantly higher ANG and TIMP-4 were observed in the severe AD group relative to the mild AD. There were different levels of plasma ANG and TIMP-4 compared with vascular dementia and other dementias. Age or gender had no major effects on levels of these proteins. Plasma ANG and TIMP-4 levels tended to be higher in ApoE ε4 carriers compared with non-carriers, but not significantly. A multiple regression analysis after adjusting for covariates revealed correlations between plasma ANG and TIMP-4 and the MMSE and CDR. Higher plasma ANG and TIMP-4 levels were associated with significant AD risk. These results demonstrate that plasma ANG and TIMP-4 may reflect the severity of cognitive function impairment, and higher levels were associated with risk of AD.

Keywords: Alzheimer's disease, angiogenin, plasma, risk, TIMP-4

DOI: 10.3233/JAD-142409

Journal: Journal of Alzheimer's Disease, vol. 45, no. 1, pp. 245-252, 2015