{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:51:59Z","timestamp":1788000719817,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      The clusterin (\n                      <jats:italic>CLU<\/jats:italic>\n                      ) gene is genetically associated with Alzheimer's disease (\n                      <jats:sc>AD<\/jats:sc>\n                      ), and CLU levels have been shown to positively correlate with regional A\u03b2 deposition in the brain, including in arteries from cerebral amyloid angiopathy (CAA) patients. CLU has also been shown to alter the aggregation, toxicity and blood\u2013brain barrier transport of amyloid beta (A\u03b2) and has therefore been suggested to play a key role in regulating the balance between A\u03b2 deposition and clearance in both the brain and cerebral blood vessels. However, it remains unclear whether the role of clusterin in relation to A\u03b2 deposition is protective or pathogenic. The aim of this study was to determine how the presence of clusterin influences the pattern of A\u03b2 deposition in hippocampal cerebral vessels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Intrahippocampal injections of fluorescent human recombinant A\u03b2 alone or in combination with human recombinant CLU were carried out in\n                      <jats:italic>Clu<\/jats:italic>\n                      knockout mice. A\u03b2 deposition and aggregate size in arterioles and capillaries were assessed by confocal microscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The presence of CLU significantly reduced the size of A\u03b2 deposits in the walls of cerebral arterioles but not in the tissue outside arterioles. There was no significant difference in overall A\u03b2 deposition within cerebral arterioles and capillaries of mice injected with A\u03b2\u2009+\u2009CLU versus A\u03b2 alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings confirm that CLU directly impacts cerebral vascular A\u03b2 aggregation, the implications of which are particularly relevant to CAA, which is a major cause of cerebral haemorrhage and cognitive decline, particularly in individuals with\n                      <jats:sc>AD<\/jats:sc>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70037","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T10:56:31Z","timestamp":1757328991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intrahippocampally Injected Human Recombinant Clusterin Reduces Amyloid\u2010\u03b2 Aggregate Size in Cerebral Arteriole Walls of Clusterin Knockout Mice"],"prefix":"10.1111","volume":"51","author":[{"given":"Alexandru","family":"Laslo","sequence":"first","affiliation":[{"name":"Department of Urology George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"},{"name":"Doctoral School of Medicine and Pharmacy George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor\u2010Gabriel","family":"Boghi\u021boiu","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"},{"name":"Psychiatry Clinic 2 Mures County Clinical Hospital  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Chinezu","sequence":"additional","affiliation":[{"name":"Department of Histology George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"},{"name":"Center for Advanced Medical and Pharmaceutical Research George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doina","family":"Manu","sequence":"additional","affiliation":[{"name":"Center for Advanced Medical and Pharmaceutical Research George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Dumitru\u00a0Ivanescu","sequence":"additional","affiliation":[{"name":"Department of Anatomy George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan\u00a0Andrei","family":"Cordo\u0219","sequence":"additional","affiliation":[{"name":"Faculty of Medicine George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"},{"name":"Centre for Experimental Medical and Imaging Studies George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00a0R.","family":"Wilson","sequence":"additional","affiliation":[{"name":"School of Science University of Wollongong  Wollongong Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Banescu","sequence":"additional","affiliation":[{"name":"Center for Advanced Medical and Pharmaceutical Research George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u00a0D.","family":"Fryer","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Verma","sequence":"additional","affiliation":[{"name":"Foundry Engineering  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-2743","authenticated-orcid":false,"given":"Jennifer\u00a0M.","family":"Dewing","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana\u2010Octavia","family":"Carare","sequence":"additional","affiliation":[{"name":"Faculty of Medicine George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219  T\u00e2rgu Mure\u0219 Romania"},{"name":"Faculty of Medicine University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","first-page":"e47","article-title":"2014 Alzheimer's Disease Facts and Figures","volume":"10","author":"Association As","year":"2014","journal-title":"Alzheimer's & Dementia"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.18.2.311"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020200068"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402043"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2002.tb00449.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.119"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.36"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00926.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00133.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0801-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041636"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4468"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-48"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.440"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600419"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0029(20000815)50:4<305::AID-JEMT10>3.0.CO;2-L"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12057"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12248"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12392"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12342"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00164"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00850-X"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162228299"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1995.1080"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7986com"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.04.012"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2191"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0157666"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02326-8"},{"issue":"33","key":"e_1_2_11_31_1","first-page":"E6962","article-title":"Loss of Clusterin Shifts Amyloid Deposition to the Cerebrovasculature via Disruption of Perivascular Drainage Pathways","volume":"114","author":"Wojtas A. M.","year":"2017","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12070"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70990-3"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6786-5_24"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-01009-1"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12070"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12392"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0498-8"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101452"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0662-1"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825e77de"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.120866"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70037","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.70037","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:18:11Z","timestamp":1772979491000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/nan.70037"],"URL":"https:\/\/doi.org\/10.1111\/nan.70037","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]},"assertion":[{"value":"2025-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70037"}}