机构：[a]Department of Neurology, Innovation Center for Neurological Disorders, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China神经内科首都医科大学宣武医院[b]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China[c]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China[d]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, P.R. China[e]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China[f]National Clinical Research Center for Geriatric Disorders, Beijing, P.R. China[g]Cerebrovascular Disease Research Institute, XuanWu Hospital, Capital Medical University, Beijing, P.R. China首都医科大学宣武医院
Alzheimer's disease (AD) and cerebrovascular disease often coexist. However, it is difficult to determine how chronic cerebral hypoperfusion affects the metabolism of amyloid-beta peptides (A beta) in a living patient with AD. Thus, we developed an animal model of this condition, using transgenic mice (PS1V97L) and right common carotid artery ligation to create chronic cerebral hypoperfusion. The metabolic processes associated with amyloid-beta peptide (A beta) were observed and evaluated in this PS1V97L plus hypoperfusion model. Compared with control mice, the model revealed significantly upregulated expression of A beta (including A beta oligomers), with decreased alpha-secretase activity and expression and increased beta-secretase activity and expression. Furthermore, the model revealed increased mRNA and protein expression of the receptor for advanced glycation end products (RAGE) and decreased mRNA and protein expression of low-density lipoprotein receptor-related protein 1 (LRP-1); both these are A beta transporters. Moreover, the model revealed decreased activity and expression of neprilysin, which is a peripheral A beta degrading enzyme. These findings suggest that hypoperfusion may magnify the effect of AD on A beta metabolism by aggravating its abnormal production, transport, and clearance.
基金：
the Key Project of the National Natural Science Foundation of China (81530036);
the National Key Scientific Instrument and Equipment Development Project (31627803);
Mission Program of Beijing Municipal Administration of Hospitals (SML20150801);
Beijing Scholars Program; Beijing Brain Initiative from Beijing Municipal Science&Technology Commission (Z161100000216137);
CHINA-CANADA Joint Initiative on Alzheimer’s Disease and Related Disorders (81261120571)
Beijing Municipal Commission of Health and Family Planning(PXM2017 026283 000002).
第一作者机构：[a]Department of Neurology, Innovation Center for Neurological Disorders, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Neurology, Innovation Center for Neurological Disorders, XuanWu Hospital, Capital Medical University, Beijing 100053, P.R. China.
推荐引用方式(GB/T 7714)：
Heyun Yang,Tingting Hou,Wei Wang,et al.The Effect of Chronic Cerebral Hypoperfusion on Amyloid-beta Metabolism in a Transgenic Mouse Model of Alzheimer's Disease (PS1V97L)[J].JOURNAL OF ALZHEIMERS DISEASE.2018,62(4):1609-1621.doi:10.3233/JAD-171094.
APA：
Heyun Yang,Tingting Hou,Wei Wang,Yumin Luo,Feng Yan&Jianping Jia.(2018).The Effect of Chronic Cerebral Hypoperfusion on Amyloid-beta Metabolism in a Transgenic Mouse Model of Alzheimer's Disease (PS1V97L).JOURNAL OF ALZHEIMERS DISEASE,62,(4)
MLA：
Heyun Yang,et al."The Effect of Chronic Cerebral Hypoperfusion on Amyloid-beta Metabolism in a Transgenic Mouse Model of Alzheimer's Disease (PS1V97L)".JOURNAL OF ALZHEIMERS DISEASE 62..4(2018):1609-1621
