title: Elevated plasma angiogenesis factors in Alzheimer's disease.
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.
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Computer Science, University of Otago, Dunedin, New Zealand.
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Min
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Cuibai
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, China Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China Beijing Municipal Key Laboratory of Geriatric Cognitive Disorders, Beijing, China Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics; D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D008609:Mental Status Schedule; D040081:Protein Array Analysis
chemical_list: D043925:Angiogenesis Inducing Agents; D001057:Apolipoproteins E; D018971:Insulin-Like Growth Factor Binding Protein 2; D004815:Epidermal Growth Factor; D020784:Matrix Metalloproteinase 8
keywords: Alzheimer's disease; TIMP-4; angiogenin; plasma; risk