Loading…
Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina
Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using nonin...
Saved in:
| Published in: | Acta neuropathologica 2020-05, Vol.139 (5), p.813-836 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3 |
| container_end_page | 836 |
| container_issue | 5 |
| container_start_page | 813 |
| container_title | Acta neuropathologica |
| container_volume | 139 |
| creator | Shi, Haoshen Koronyo, Yosef Rentsendorj, Altan Regis, Giovanna C. Sheyn, Julia Fuchs, Dieu-Trang Kramerov, Andrei A. Ljubimov, Alexander V. Dumitrascu, Oana M. Rodriguez, Anthony R. Barron, Ernesto Hinton, David R. Black, Keith L. Miller, Carol A. Mirzaei, Nazanin Koronyo-Hamaoui, Maya |
| description | Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ
40
and Aβ
42
burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ
40
levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy. |
| doi_str_mv | 10.1007/s00401-020-02134-w |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7181564</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A621829659</galeid><sourcerecordid>A621829659</sourcerecordid><originalsourceid>FETCH-LOGICAL-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3</originalsourceid><addsrcrecordid>eNp9kt9qFDEUxgdR7Fp9AS8k4I03U_M_MzfCUqwWCt7oreFs5sw2ZSZZk5mW7ZWv4ev1Scy6tbUiEkJIzu_7wkm-qnrJ6BGj1LzNlErKasppmUzI-upRtWBS8JoqIR5XC0pLWQvOD6pnOV-UHTdSPa0OBKdSMM0X1dfTDsPke-9g8jGQ2BOENGzJBpN32wnJEHMmEDpyCdnNAyQC43aIvovZZ-IDWQ7X5-hHTDfff2TS-YyQkSScfIDn1ZMehowvbtfD6svJ-8_HH-uzTx9Oj5dntdPUTLVy0hmJoNFgr7nuTTlYSQ0cALhWRmsGDoEK7lZsxWirmk61znQOtOhRHFbv9r6beTVi50pPCQa7SX6EtLURvH1YCf7cruOlNaxhSsti8ObWIMVvM-bJjj47HAYIGOdsuVBCNU3Ddujrv9CLOKdQ2itUK1otlTT31BoGtD70sdzrdqZ2qTlreKtVW6ijf1BldDh6FwP2vpw_EPC9wKXyLwn7ux4ZtbtU2H0qbEmF_ZUKe1VEr_58nTvJ7xgUQOyBXEphjem-pf_Y_gSeTMTF</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2393964547</pqid></control><display><type>article</type><title>Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina</title><source>Springer Link</source><creator>Shi, Haoshen ; Koronyo, Yosef ; Rentsendorj, Altan ; Regis, Giovanna C. ; Sheyn, Julia ; Fuchs, Dieu-Trang ; Kramerov, Andrei A. ; Ljubimov, Alexander V. ; Dumitrascu, Oana M. ; Rodriguez, Anthony R. ; Barron, Ernesto ; Hinton, David R. ; Black, Keith L. ; Miller, Carol A. ; Mirzaei, Nazanin ; Koronyo-Hamaoui, Maya</creator><creatorcontrib>Shi, Haoshen ; Koronyo, Yosef ; Rentsendorj, Altan ; Regis, Giovanna C. ; Sheyn, Julia ; Fuchs, Dieu-Trang ; Kramerov, Andrei A. ; Ljubimov, Alexander V. ; Dumitrascu, Oana M. ; Rodriguez, Anthony R. ; Barron, Ernesto ; Hinton, David R. ; Black, Keith L. ; Miller, Carol A. ; Mirzaei, Nazanin ; Koronyo-Hamaoui, Maya</creatorcontrib><description>Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ
40
and Aβ
42
burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ
40
levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.</description><identifier>ISSN: 0001-6322</identifier><identifier>EISSN: 1432-0533</identifier><identifier>DOI: 10.1007/s00401-020-02134-w</identifier><identifier>PMID: 32043162</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Advertising executives ; Aged ; Aged, 80 and over ; Alzheimer Disease - pathology ; Alzheimer's disease ; Amyloid beta-Peptides - metabolism ; Amyloid beta-protein ; Amyloid beta-Protein Precursor - metabolism ; Amyloidosis ; Amyloidosis - complications ; Amyloidosis - pathology ; Angiography ; Apoptosis ; Autopsy ; Blood-brain barrier ; Blood-Brain Barrier - pathology ; Brain - pathology ; Cerebral amyloid angiopathy ; Cerebral Amyloid Angiopathy - pathology ; Cognition - physiology ; Cognitive ability ; Diagnostic imaging ; Female ; Humans ; Male ; Medical colleges ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Microvasculature ; Molecular modelling ; Neurodegenerative diseases ; Neuroimaging ; Neurosciences ; Original Paper ; Pathology ; Pericytes ; Pericytes - pathology ; Platelet-derived growth factor ; Retina ; Retina - pathology ; Risk factors</subject><ispartof>Acta neuropathologica, 2020-05, Vol.139 (5), p.813-836</ispartof><rights>The Author(s) 2020</rights><rights>COPYRIGHT 2020 Springer</rights><rights>The Author(s) 2020. 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-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3</citedby><cites>FETCH-LOGICAL-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3</cites><orcidid>0000-0003-2864-8442</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32043162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Haoshen</creatorcontrib><creatorcontrib>Koronyo, Yosef</creatorcontrib><creatorcontrib>Rentsendorj, Altan</creatorcontrib><creatorcontrib>Regis, Giovanna C.</creatorcontrib><creatorcontrib>Sheyn, Julia</creatorcontrib><creatorcontrib>Fuchs, Dieu-Trang</creatorcontrib><creatorcontrib>Kramerov, Andrei A.</creatorcontrib><creatorcontrib>Ljubimov, Alexander V.</creatorcontrib><creatorcontrib>Dumitrascu, Oana M.</creatorcontrib><creatorcontrib>Rodriguez, Anthony R.</creatorcontrib><creatorcontrib>Barron, Ernesto</creatorcontrib><creatorcontrib>Hinton, David R.</creatorcontrib><creatorcontrib>Black, Keith L.</creatorcontrib><creatorcontrib>Miller, Carol A.</creatorcontrib><creatorcontrib>Mirzaei, Nazanin</creatorcontrib><creatorcontrib>Koronyo-Hamaoui, Maya</creatorcontrib><title>Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina</title><title>Acta neuropathologica</title><addtitle>Acta Neuropathol</addtitle><addtitle>Acta Neuropathol</addtitle><description>Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ
40
and Aβ
42
burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ
40
levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.</description><subject>Advertising executives</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-protein</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloidosis</subject><subject>Amyloidosis - complications</subject><subject>Amyloidosis - pathology</subject><subject>Angiography</subject><subject>Apoptosis</subject><subject>Autopsy</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - pathology</subject><subject>Brain - pathology</subject><subject>Cerebral amyloid angiopathy</subject><subject>Cerebral Amyloid Angiopathy - pathology</subject><subject>Cognition - physiology</subject><subject>Cognitive ability</subject><subject>Diagnostic imaging</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical colleges</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Microvasculature</subject><subject>Molecular modelling</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Neurosciences</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>Pericytes</subject><subject>Pericytes - pathology</subject><subject>Platelet-derived growth factor</subject><subject>Retina</subject><subject>Retina - pathology</subject><subject>Risk factors</subject><issn>0001-6322</issn><issn>1432-0533</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kt9qFDEUxgdR7Fp9AS8k4I03U_M_MzfCUqwWCt7oreFs5sw2ZSZZk5mW7ZWv4ev1Scy6tbUiEkJIzu_7wkm-qnrJ6BGj1LzNlErKasppmUzI-upRtWBS8JoqIR5XC0pLWQvOD6pnOV-UHTdSPa0OBKdSMM0X1dfTDsPke-9g8jGQ2BOENGzJBpN32wnJEHMmEDpyCdnNAyQC43aIvovZZ-IDWQ7X5-hHTDfff2TS-YyQkSScfIDn1ZMehowvbtfD6svJ-8_HH-uzTx9Oj5dntdPUTLVy0hmJoNFgr7nuTTlYSQ0cALhWRmsGDoEK7lZsxWirmk61znQOtOhRHFbv9r6beTVi50pPCQa7SX6EtLURvH1YCf7cruOlNaxhSsti8ObWIMVvM-bJjj47HAYIGOdsuVBCNU3Ddujrv9CLOKdQ2itUK1otlTT31BoGtD70sdzrdqZ2qTlreKtVW6ijf1BldDh6FwP2vpw_EPC9wKXyLwn7ux4ZtbtU2H0qbEmF_ZUKe1VEr_58nTvJ7xgUQOyBXEphjem-pf_Y_gSeTMTF</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Shi, Haoshen</creator><creator>Koronyo, Yosef</creator><creator>Rentsendorj, Altan</creator><creator>Regis, Giovanna C.</creator><creator>Sheyn, Julia</creator><creator>Fuchs, Dieu-Trang</creator><creator>Kramerov, Andrei A.</creator><creator>Ljubimov, Alexander V.</creator><creator>Dumitrascu, Oana M.</creator><creator>Rodriguez, Anthony R.</creator><creator>Barron, Ernesto</creator><creator>Hinton, David R.</creator><creator>Black, Keith L.</creator><creator>Miller, Carol A.</creator><creator>Mirzaei, Nazanin</creator><creator>Koronyo-Hamaoui, Maya</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2864-8442</orcidid></search><sort><creationdate>20200501</creationdate><title>Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina</title><author>Shi, Haoshen ; Koronyo, Yosef ; Rentsendorj, Altan ; Regis, Giovanna C. ; Sheyn, Julia ; Fuchs, Dieu-Trang ; Kramerov, Andrei A. ; Ljubimov, Alexander V. ; Dumitrascu, Oana M. ; Rodriguez, Anthony R. ; Barron, Ernesto ; Hinton, David R. ; Black, Keith L. ; Miller, Carol A. ; Mirzaei, Nazanin ; Koronyo-Hamaoui, Maya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Advertising executives</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-protein</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloidosis</topic><topic>Amyloidosis - complications</topic><topic>Amyloidosis - pathology</topic><topic>Angiography</topic><topic>Apoptosis</topic><topic>Autopsy</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - pathology</topic><topic>Brain - pathology</topic><topic>Cerebral amyloid angiopathy</topic><topic>Cerebral Amyloid Angiopathy - pathology</topic><topic>Cognition - physiology</topic><topic>Cognitive ability</topic><topic>Diagnostic imaging</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical colleges</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Experimental</topic><topic>Microvasculature</topic><topic>Molecular modelling</topic><topic>Neurodegenerative diseases</topic><topic>Neuroimaging</topic><topic>Neurosciences</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Pericytes</topic><topic>Pericytes - pathology</topic><topic>Platelet-derived growth factor</topic><topic>Retina</topic><topic>Retina - pathology</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Haoshen</creatorcontrib><creatorcontrib>Koronyo, Yosef</creatorcontrib><creatorcontrib>Rentsendorj, Altan</creatorcontrib><creatorcontrib>Regis, Giovanna C.</creatorcontrib><creatorcontrib>Sheyn, Julia</creatorcontrib><creatorcontrib>Fuchs, Dieu-Trang</creatorcontrib><creatorcontrib>Kramerov, Andrei A.</creatorcontrib><creatorcontrib>Ljubimov, Alexander V.</creatorcontrib><creatorcontrib>Dumitrascu, Oana M.</creatorcontrib><creatorcontrib>Rodriguez, Anthony R.</creatorcontrib><creatorcontrib>Barron, Ernesto</creatorcontrib><creatorcontrib>Hinton, David R.</creatorcontrib><creatorcontrib>Black, Keith L.</creatorcontrib><creatorcontrib>Miller, Carol A.</creatorcontrib><creatorcontrib>Mirzaei, Nazanin</creatorcontrib><creatorcontrib>Koronyo-Hamaoui, Maya</creatorcontrib><collection>Springer_OA刊</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</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>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta neuropathologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Haoshen</au><au>Koronyo, Yosef</au><au>Rentsendorj, Altan</au><au>Regis, Giovanna C.</au><au>Sheyn, Julia</au><au>Fuchs, Dieu-Trang</au><au>Kramerov, Andrei A.</au><au>Ljubimov, Alexander V.</au><au>Dumitrascu, Oana M.</au><au>Rodriguez, Anthony R.</au><au>Barron, Ernesto</au><au>Hinton, David R.</au><au>Black, Keith L.</au><au>Miller, Carol A.</au><au>Mirzaei, Nazanin</au><au>Koronyo-Hamaoui, Maya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina</atitle><jtitle>Acta neuropathologica</jtitle><stitle>Acta Neuropathol</stitle><addtitle>Acta Neuropathol</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>139</volume><issue>5</issue><spage>813</spage><epage>836</epage><pages>813-836</pages><issn>0001-6322</issn><eissn>1432-0533</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ
40
and Aβ
42
burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ
40
levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32043162</pmid><doi>10.1007/s00401-020-02134-w</doi><tpages>24</tpages><orcidid>https://orcid.org/0000-0003-2864-8442</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0001-6322 |
| ispartof | Acta neuropathologica, 2020-05, Vol.139 (5), p.813-836 |
| issn | 0001-6322 1432-0533 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7181564 |
| source | Springer Link |
| subjects | Advertising executives Aged Aged, 80 and over Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism Amyloid beta-protein Amyloid beta-Protein Precursor - metabolism Amyloidosis Amyloidosis - complications Amyloidosis - pathology Angiography Apoptosis Autopsy Blood-brain barrier Blood-Brain Barrier - pathology Brain - pathology Cerebral amyloid angiopathy Cerebral Amyloid Angiopathy - pathology Cognition - physiology Cognitive ability Diagnostic imaging Female Humans Male Medical colleges Medical research Medicine Medicine & Public Health Medicine, Experimental Microvasculature Molecular modelling Neurodegenerative diseases Neuroimaging Neurosciences Original Paper Pathology Pericytes Pericytes - pathology Platelet-derived growth factor Retina Retina - pathology Risk factors |
| title | Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T08%3A45%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20of%20early%20pericyte%20loss%20and%20vascular%20amyloidosis%20in%20Alzheimer%E2%80%99s%20disease%20retina&rft.jtitle=Acta%20neuropathologica&rft.au=Shi,%20Haoshen&rft.date=2020-05-01&rft.volume=139&rft.issue=5&rft.spage=813&rft.epage=836&rft.pages=813-836&rft.issn=0001-6322&rft.eissn=1432-0533&rft_id=info:doi/10.1007/s00401-020-02134-w&rft_dat=%3Cgale_pubme%3EA621829659%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c607t-5c4c74ea6e7ef626f7c4cb46a2aaa2657661acea032cb1b10958d59c7dca63fe3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2393964547&rft_id=info:pmid/32043162&rft_galeid=A621829659&rfr_iscdi=true |