{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:32:10Z","timestamp":1775100730873,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00275"],"award-info":[{"award-number":["PI17\/00275"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00465"],"award-info":[{"award-number":["PI20\/00465"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genome\u2010wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, <jats:italic>CD2AP<\/jats:italic> encodes CD2\u2010associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Although a clear link between CD2AP defects and glomerular pathology has been described, little is known about the function of CD2AP in the brain. The aim of this study was to analyze the distribution of CD2AP in the AD brain and its potential associations with tau aggregation and \u03b2\u2010amyloid (A\u03b2) deposition. First, we performed immunohistochemical analysis of CD2AP expression in brain tissue from AD patients and controls (<jats:italic>N<\/jats:italic>\u00a0=\u00a060). Our results showed granular CD2AP immunoreactivity in the human brain endothelium in all samples. In AD cases, no CD2AP was found to be associated with A\u03b2 deposits in vessels or parenchymal plaques. CD2AP neuronal inclusions similar to neurofibrillary tangles (NFT) and neuropil thread\u2010like deposits were found only in AD samples. Moreover, immunofluorescence analysis revealed that CD2AP colocalized with pTau. Regarding CD2AP neuronal distribution, a hierarchical progression from the entorhinal to the temporal and occipital cortex was detected. We found that CD2AP immunodetection in neurons was strongly and positively associated with Braak neurofibrillary stage, independent of age and other pathological hallmarks. To further investigate the association between pTau and CD2AP, we included samples from cases of primary tauopathies (corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Pick's disease [PiD]) in our study. Among these cases, CD2AP positivity was only found in PiD samples as neurofibrillary tangle\u2010like and Pick body\u2010like deposits, whereas no neuronal CD2AP deposits were detected in PSP or CBD samples, which suggested an association of CD2AP neuronal expression with 3R\u2010Tau\u2010diseases. In conclusion, our findings open a new road to investigate the complex cellular mechanism underlying the tangle conformation and tau pathology in the brain.<\/jats:p>","DOI":"10.1111\/bpa.13016","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T07:00:19Z","timestamp":1631516419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer\u2019s disease"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-8274","authenticated-orcid":false,"given":"Jessica","family":"Camacho","sequence":"first","affiliation":[{"name":"Pathology Department Vall d\u2019Hebron University Hospital Barcelona Spain"},{"name":"Morphological Science Department Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9320-6566","authenticated-orcid":false,"given":"Alberto","family":"R\u00e1bano","sequence":"additional","affiliation":[{"name":"Neuropathology Department CIEN Foundation Alzheimer\u2019s Centre Queen Sof\u00eda Foundation Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-5242","authenticated-orcid":false,"given":"Paula","family":"Marazuela","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory Vall d\u2019Hebron Research Institute Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1480-622X","authenticated-orcid":false,"given":"Anna","family":"Bonaterra\u2010Pastra","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory Vall d\u2019Hebron Research Institute Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2666-0982","authenticated-orcid":false,"given":"Garazi","family":"Serna","sequence":"additional","affiliation":[{"name":"Morphological Science Department Universitat Autonoma de Barcelona Barcelona Spain"},{"name":"Molecular Oncology Group Vall d\u2019Hebron Institute of Oncology (VHIO) Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4912-5114","authenticated-orcid":false,"given":"Teresa","family":"Molin\u00e9","sequence":"additional","affiliation":[{"name":"Pathology Department Vall d\u2019Hebron University Hospital Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-1390","authenticated-orcid":false,"given":"Santiago","family":"Ram\u00f3n y Cajal","sequence":"additional","affiliation":[{"name":"Pathology Department Vall d\u2019Hebron University Hospital Barcelona Spain"},{"name":"Morphological Science Department Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6004-5364","authenticated-orcid":false,"given":"Elena","family":"Mart\u00ednez\u2010S\u00e1ez","sequence":"additional","affiliation":[{"name":"Pathology Department Vall d\u2019Hebron University Hospital Barcelona Spain"},{"name":"Morphological Science Department Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8844-0091","authenticated-orcid":false,"given":"Mar","family":"Hern\u00e1ndez\u2010Guillamon","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory Vall d\u2019Hebron Research Institute Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"World Alzheimer report 2019","year":"2019"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2016.08.018"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.58.12.1791"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.41.4.479"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010006\u20100127\u2010z"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0166\u20102236(98)01337\u2010x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2015"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12208"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170116143743"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.42.3.631"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21223"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.09.001"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825018f7"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006075"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.1424"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531\u20108249(199903)45:3<358:aid\u2010ana12>3.0.co;2\u2010x"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.04.002"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm104"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12825"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211851"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.803"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010019\u20100358\u20102"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010019\u20100323\u20107"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2423\u201015.2016"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20100436.2007.00255.x"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.4.F785"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1210\u20101248"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn712"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00016"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000755\u20107"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.801"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.2815"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004606"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.20"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.03.013"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010014\u20108834\u20102"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010021\u201000163\u20106"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2020.07.002"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)81608\u20106"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5438.312"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.202390"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)63080\u20105"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.4238\/2014.November.11.16"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn208"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.4137\/CCRep.S30867"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.006"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3407"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010015\u20100006\u2010y"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201642738"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.005385"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt478"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.041"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010180512"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24277"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010013\u20101111\u2010z"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.05.017"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010020\u201002125\u2010x"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.586731"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073018"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.027"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.1999.0721243.x"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072\u2010199602000\u201000004"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101789.2006.00669.x"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12108"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9649"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000128091.92139.0f"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.4421"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201006783\u20100"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157\u2010016\u20101257\u20109"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.13016","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bpa.13016","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.13016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T20:37:57Z","timestamp":1692391077000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.13016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,12]]},"references-count":74,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1111\/bpa.13016"],"URL":"https:\/\/doi.org\/10.1111\/bpa.13016","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,12]]},"assertion":[{"value":"2021-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13016"}}