Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease
Abstract Background Alzheimer’s disease (AD) is characterized by the deposition of amyloid-β (Aβ) in brain parenchyma and cerebral blood vessels as cerebral amyloid angiopathy (CAA). Clusterin, a chaperon protein associated with Aβ aggregation, toxicity and transport through blood–brain barrier, may...
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doaj-b9324b41338149a9b4f82345318575fa2020-11-24T21:34:37ZengBMCBMC Neuroscience1471-22022018-01-011911910.1186/s12868-018-0402-7Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s diseaseXue-Mei Qi0Cheng Wang1Xing-Kun Chu2Gen Li3Jian-Fang Ma4Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineAbstract Background Alzheimer’s disease (AD) is characterized by the deposition of amyloid-β (Aβ) in brain parenchyma and cerebral blood vessels as cerebral amyloid angiopathy (CAA). Clusterin, a chaperon protein associated with Aβ aggregation, toxicity and transport through blood–brain barrier, may play a key role in the development of AD. Recently, clusterin peptide D-[113–122] was shown to mimic clusterin’s function and exerted therapeutic effect in atherosclerosis. In this study, we investigated whether this clusterin peptide also affected (Aβ) deposition in AD transgenic mouse. Results Using a micropump, synthetic peptide 113–122 of clusterin protein (20 μg/200 μl) was infused into the lateral ventricle of 8-month 5 × FAD transgenic mouse model (Tg6799), for 2 weeks. Water-maze testing showed an improved cognitive function of the Tg6799 mice treated with clusterin. Immunocytochemistry and quantitative analysis revealed that intraventricular (icv) administration of clusterin peptide in Tg6799 mouse reduced Aβ plaques as well the severity of cerebral amyloid angiopathy. Enzyme-linked immunosorbent assay demonstrated a decreased in the soluble levels of Aβ (Aβ40 and Aβ42) in the brain. Western-blot revealed an increased level of LRP-2 after clusterin peptide treatment. Conclusion These results suggest that icv infusion of clusterin peptide D-[113–122] offers a promising therapeutic approach to reduce Aβ deposition as well as CAA. The LRP2-mediated clearance system might be involved in the mechanism of these effects.http://link.springer.com/article/10.1186/s12868-018-0402-7ClusterinAlzheimer’s diseaseLRP-2Amyloid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xue-Mei Qi Cheng Wang Xing-Kun Chu Gen Li Jian-Fang Ma |
spellingShingle |
Xue-Mei Qi Cheng Wang Xing-Kun Chu Gen Li Jian-Fang Ma Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease BMC Neuroscience Clusterin Alzheimer’s disease LRP-2 Amyloid |
author_facet |
Xue-Mei Qi Cheng Wang Xing-Kun Chu Gen Li Jian-Fang Ma |
author_sort |
Xue-Mei Qi |
title |
Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease |
title_short |
Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease |
title_full |
Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease |
title_fullStr |
Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease |
title_full_unstemmed |
Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer’s disease |
title_sort |
intraventricular infusion of clusterin ameliorated cognition and pathology in tg6799 model of alzheimer’s disease |
publisher |
BMC |
series |
BMC Neuroscience |
issn |
1471-2202 |
publishDate |
2018-01-01 |
description |
Abstract Background Alzheimer’s disease (AD) is characterized by the deposition of amyloid-β (Aβ) in brain parenchyma and cerebral blood vessels as cerebral amyloid angiopathy (CAA). Clusterin, a chaperon protein associated with Aβ aggregation, toxicity and transport through blood–brain barrier, may play a key role in the development of AD. Recently, clusterin peptide D-[113–122] was shown to mimic clusterin’s function and exerted therapeutic effect in atherosclerosis. In this study, we investigated whether this clusterin peptide also affected (Aβ) deposition in AD transgenic mouse. Results Using a micropump, synthetic peptide 113–122 of clusterin protein (20 μg/200 μl) was infused into the lateral ventricle of 8-month 5 × FAD transgenic mouse model (Tg6799), for 2 weeks. Water-maze testing showed an improved cognitive function of the Tg6799 mice treated with clusterin. Immunocytochemistry and quantitative analysis revealed that intraventricular (icv) administration of clusterin peptide in Tg6799 mouse reduced Aβ plaques as well the severity of cerebral amyloid angiopathy. Enzyme-linked immunosorbent assay demonstrated a decreased in the soluble levels of Aβ (Aβ40 and Aβ42) in the brain. Western-blot revealed an increased level of LRP-2 after clusterin peptide treatment. Conclusion These results suggest that icv infusion of clusterin peptide D-[113–122] offers a promising therapeutic approach to reduce Aβ deposition as well as CAA. The LRP2-mediated clearance system might be involved in the mechanism of these effects. |
topic |
Clusterin Alzheimer’s disease LRP-2 Amyloid |
url |
http://link.springer.com/article/10.1186/s12868-018-0402-7 |
work_keys_str_mv |
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