Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis
Background A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to i...
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| Veröffentlicht in: | Aging cell 2022-01, Vol.21 (1), p.e13533-n/a |
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| creator | Yu, Zhong‐Yuan Chen, Dong‐Wan Tan, Cheng‐Rong Zeng, Gui‐Hua He, Chen‐Yang Wang, Jun Bu, Xian‐Le Wang, Yan‐Jiang |
| description | Background
A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery.
Methods
We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice.
Results
We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD‐related pathologies in AD mice.
Conclusion
Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.
Our study reveals the physiological capacity of the spleen to clear circulating Aβ, and the splenectomy aggravates Alzheimer‐type pathogenesis in APP/PS1 transgenic mice. |
| doi_str_mv | 10.1111/acel.13533 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8761003</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2619766395</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4893-7697db885618c5fdec73155bda3c9f9c7eca75fee5e24b7643b2776e1c8dab623</originalsourceid><addsrcrecordid>eNp9kcFq3DAQhkVpSNIklz5AEfRSCptali1Zl8KypE1gITk0ZzGWx14F2XIlb4pzyiPkWfIgfYg-SbzZdGl76FxmQB8fM_oJecuSUzbVJzDoThnPOX9FDlkms5mSqXi9m1lxQN7EeJMkTKqE75MDnimuJM8OCVytxmi984014KhxCAE6g9TXdP7zkZYjjb1D7Ch01fPYoRl8O1JomgC3MGCkc3e3Qtti-HX_MIw90h6GlW8mNNp4TPZqcBFPXvoRuf5y9m1xPltefr1YzJczkxWKz6RQsiqLIhesMHldoZGc5XlZATeqVkaiAZnXiDmmWSlFxstUSoHMFBWUIuVH5PPW26_LFiuD3RDA6T7YFsKoPVj990tnV7rxt7qQgiUJnwQfXgTBf19jHHRr4_S1Djr066hTwXiqeMo26Pt_0Bu_Dt103oZSUgiu8on6uKVM8DEGrHfLsERvktOb5PRzchP87s_1d-jvqCaAbYEf1uH4H5WeL86WW-kTCW6nkw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2619766395</pqid></control><display><type>article</type><title>Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via Wiley Online Library</source><source>Wiley Online Library Open Access</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Yu, Zhong‐Yuan ; Chen, Dong‐Wan ; Tan, Cheng‐Rong ; Zeng, Gui‐Hua ; He, Chen‐Yang ; Wang, Jun ; Bu, Xian‐Le ; Wang, Yan‐Jiang</creator><creatorcontrib>Yu, Zhong‐Yuan ; Chen, Dong‐Wan ; Tan, Cheng‐Rong ; Zeng, Gui‐Hua ; He, Chen‐Yang ; Wang, Jun ; Bu, Xian‐Le ; Wang, Yan‐Jiang</creatorcontrib><description>Background
A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery.
Methods
We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice.
Results
We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD‐related pathologies in AD mice.
Conclusion
Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.
Our study reveals the physiological capacity of the spleen to clear circulating Aβ, and the splenectomy aggravates Alzheimer‐type pathogenesis in APP/PS1 transgenic mice.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.13533</identifier><identifier>PMID: 34939734</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Alzheimer Disease - pathology ; Alzheimer's disease ; Amyloid beta-Peptides - adverse effects ; Animals ; Aβ burden ; behaviour deficits ; Disease Models, Animal ; Female ; Humans ; Hypersplenism ; Immune clearance ; Macrophages ; Mice ; Mice, Transgenic ; Monocytes ; Original Paper ; Original Papers ; Physiology ; Presenilin 1 ; Spleen ; Spleen - pathology ; Splenectomy ; Splenectomy - methods ; Splenic artery</subject><ispartof>Aging cell, 2022-01, Vol.21 (1), p.e13533-n/a</ispartof><rights>2021 The Authors. published by Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4893-7697db885618c5fdec73155bda3c9f9c7eca75fee5e24b7643b2776e1c8dab623</citedby><cites>FETCH-LOGICAL-c4893-7697db885618c5fdec73155bda3c9f9c7eca75fee5e24b7643b2776e1c8dab623</cites><orcidid>0000-0002-6227-6112</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761003/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761003/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34939734$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Zhong‐Yuan</creatorcontrib><creatorcontrib>Chen, Dong‐Wan</creatorcontrib><creatorcontrib>Tan, Cheng‐Rong</creatorcontrib><creatorcontrib>Zeng, Gui‐Hua</creatorcontrib><creatorcontrib>He, Chen‐Yang</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Bu, Xian‐Le</creatorcontrib><creatorcontrib>Wang, Yan‐Jiang</creatorcontrib><title>Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Background
A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery.
Methods
We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice.
Results
We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD‐related pathologies in AD mice.
Conclusion
Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.
Our study reveals the physiological capacity of the spleen to clear circulating Aβ, and the splenectomy aggravates Alzheimer‐type pathogenesis in APP/PS1 transgenic mice.</description><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - adverse effects</subject><subject>Animals</subject><subject>Aβ burden</subject><subject>behaviour deficits</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Humans</subject><subject>Hypersplenism</subject><subject>Immune clearance</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Monocytes</subject><subject>Original Paper</subject><subject>Original Papers</subject><subject>Physiology</subject><subject>Presenilin 1</subject><subject>Spleen</subject><subject>Spleen - pathology</subject><subject>Splenectomy</subject><subject>Splenectomy - methods</subject><subject>Splenic artery</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kcFq3DAQhkVpSNIklz5AEfRSCptali1Zl8KypE1gITk0ZzGWx14F2XIlb4pzyiPkWfIgfYg-SbzZdGl76FxmQB8fM_oJecuSUzbVJzDoThnPOX9FDlkms5mSqXi9m1lxQN7EeJMkTKqE75MDnimuJM8OCVytxmi984014KhxCAE6g9TXdP7zkZYjjb1D7Ch01fPYoRl8O1JomgC3MGCkc3e3Qtti-HX_MIw90h6GlW8mNNp4TPZqcBFPXvoRuf5y9m1xPltefr1YzJczkxWKz6RQsiqLIhesMHldoZGc5XlZATeqVkaiAZnXiDmmWSlFxstUSoHMFBWUIuVH5PPW26_LFiuD3RDA6T7YFsKoPVj990tnV7rxt7qQgiUJnwQfXgTBf19jHHRr4_S1Djr066hTwXiqeMo26Pt_0Bu_Dt103oZSUgiu8on6uKVM8DEGrHfLsERvktOb5PRzchP87s_1d-jvqCaAbYEf1uH4H5WeL86WW-kTCW6nkw</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Yu, Zhong‐Yuan</creator><creator>Chen, Dong‐Wan</creator><creator>Tan, Cheng‐Rong</creator><creator>Zeng, Gui‐Hua</creator><creator>He, Chen‐Yang</creator><creator>Wang, Jun</creator><creator>Bu, Xian‐Le</creator><creator>Wang, Yan‐Jiang</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6227-6112</orcidid></search><sort><creationdate>202201</creationdate><title>Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis</title><author>Yu, Zhong‐Yuan ; Chen, Dong‐Wan ; Tan, Cheng‐Rong ; Zeng, Gui‐Hua ; He, Chen‐Yang ; Wang, Jun ; Bu, Xian‐Le ; Wang, Yan‐Jiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4893-7697db885618c5fdec73155bda3c9f9c7eca75fee5e24b7643b2776e1c8dab623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - adverse effects</topic><topic>Animals</topic><topic>Aβ burden</topic><topic>behaviour deficits</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Humans</topic><topic>Hypersplenism</topic><topic>Immune clearance</topic><topic>Macrophages</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Monocytes</topic><topic>Original Paper</topic><topic>Original Papers</topic><topic>Physiology</topic><topic>Presenilin 1</topic><topic>Spleen</topic><topic>Spleen - pathology</topic><topic>Splenectomy</topic><topic>Splenectomy - methods</topic><topic>Splenic artery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Zhong‐Yuan</creatorcontrib><creatorcontrib>Chen, Dong‐Wan</creatorcontrib><creatorcontrib>Tan, Cheng‐Rong</creatorcontrib><creatorcontrib>Zeng, Gui‐Hua</creatorcontrib><creatorcontrib>He, Chen‐Yang</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Bu, Xian‐Le</creatorcontrib><creatorcontrib>Wang, Yan‐Jiang</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Zhong‐Yuan</au><au>Chen, Dong‐Wan</au><au>Tan, Cheng‐Rong</au><au>Zeng, Gui‐Hua</au><au>He, Chen‐Yang</au><au>Wang, Jun</au><au>Bu, Xian‐Le</au><au>Wang, Yan‐Jiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2022-01</date><risdate>2022</risdate><volume>21</volume><issue>1</issue><spage>e13533</spage><epage>n/a</epage><pages>e13533-n/a</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>Background
A previous study demonstrated that nearly 40%–60% of brain Aβ flows out into the peripheral system for clearance. However, where and how circulating Aβ is cleared in the periphery remains unclear. The spleen acts as a blood filter and an immune organ. The aim of the present study was to investigate the role of the spleen in the clearance of Aβ in the periphery.
Methods
We investigated the physiological clearance of Aβ by the spleen and established a mouse model of AD and spleen excision by removing the spleens of APP/PS1 mice to investigate the effect of splenectomy on AD mice.
Results
We found that Aβ levels in the splenic artery were higher than those in the splenic vein, suggesting that circulating Aβ is cleared when blood flows through the spleen. Next, we found that splenic monocytes/macrophages could take up Aβ directly in vivo and in vitro. Splenectomy aggravated behaviour deficits, brain Aβ burden and AD‐related pathologies in AD mice.
Conclusion
Our study reveals for the first time that the spleen exerts a physiological function of clearing circulating Aβ in the periphery. Our study also suggests that splenectomy, which is a routine treatment for splenic rupture and hypersplenism, might accelerate the development of AD.
Our study reveals the physiological capacity of the spleen to clear circulating Aβ, and the splenectomy aggravates Alzheimer‐type pathogenesis in APP/PS1 transgenic mice.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>34939734</pmid><doi>10.1111/acel.13533</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-6227-6112</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library; Wiley Online Library Open Access; PubMed Central; Alma/SFX Local Collection |
| subjects | Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - adverse effects Animals Aβ burden behaviour deficits Disease Models, Animal Female Humans Hypersplenism Immune clearance Macrophages Mice Mice, Transgenic Monocytes Original Paper Original Papers Physiology Presenilin 1 Spleen Spleen - pathology Splenectomy Splenectomy - methods Splenic artery |
| title | Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis |
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