{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:49:42Z","timestamp":1790678982873,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008599","name":"Alzheimerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008599","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007464","name":"Torsten S\u00f6derbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007464","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010773","name":"Demensf\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010773","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory dysfunction and cognitive decline. Pathological aging (PA) describes patients who are amyloid\u2010positive but cognitively unimpaired at time of death. Both AD and PA contain amyloid plaques dominated by amyloid \u03b2 (A\u03b2) peptides. In this study, we investigated and compared synaptic protein levels, amyloid plaque load, and A\u03b2 peptide patterns between AD and PA. Two cohorts of post\u2010mortem brain tissue were investigated. In the first, consisting of controls, PA, AD, and familial AD (FAD) individuals, synaptic proteins extracted with tris(hydroxymethyl)aminomethane\u2010buffered saline (TBS) were analyzed. In the second, consisting of tissue from AD and PA patients from three different regions (occipital lobe, frontal lobe, and cerebellum), a two\u2010step extraction was performed. Five synaptic proteins were extracted using TBS, and from the remaining portion A\u03b2 peptides were extracted using formic acid. Subsequently, immunoprecipitation with several antibodies targeting different proteins\/peptides was performed for both fractions, which were subsequently analyzed by mass spectrometry. The levels of synaptic proteins were lower in AD (and FAD) compared with PA (and controls), confirming synaptic loss in AD patients. The amyloid plaque load was increased in AD compared with PA, and the <jats:italic>relative<\/jats:italic> amount of A\u03b240 was higher in AD while for A\u03b242 it was higher in PA. In AD loss of synaptic function was associated with increased plaque load and increased amounts of A\u03b240 compared with PA cases, suggesting that synaptic function is preserved in PA cases even in the presence of A\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15487-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15487","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T14:21:50Z","timestamp":1630592510000},"page":"258-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Amyloid pathology and synaptic loss in pathological aging"],"prefix":"10.1111","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4443-2836","authenticated-orcid":false,"given":"Eleni","family":"Gkanatsiou","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina E.","family":"Toomey","sequence":"additional","affiliation":[{"name":"The Queen Square Brain Bank for Neurological Disorders Department of Clinical and Movement Neurosciences UCL Institute of Neurology London UK"},{"name":"UK Dementia Research Institute at UCL London UK"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Vrillon","sequence":"additional","affiliation":[{"name":"Center of Cognitive Neurology Lariboisi\u00e8re Fernand\u2010Widal Hospital APHP University of Paris Diderot Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hlin","family":"Kvartsberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Portelius","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"},{"name":"UK Dementia Research Institute at UCL London UK"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Brinkmalm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammaryn","family":"Lashley","sequence":"additional","affiliation":[{"name":"The Queen Square Brain Bank for Neurological Disorders Department of Clinical and Movement Neurosciences UCL Institute of Neurology London UK"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Brinkmalm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01137.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06813-x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-53"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.040113"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.040113"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz066"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.2987"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.11.006"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0564-2"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179941"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12015-w"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610298005110"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/ana.10069","article-title":"Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment","volume":"51","author":"DeKosky S. T.","year":"2002","journal-title":"Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.10.011"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.11.002"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.02.033"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02175-1"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42833-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370305"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90458-8"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90458-8"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1910-3"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2214"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/oms.1210290410"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.006604"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1236-13.2013"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0910-3"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41896-0"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006338"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.18.8378"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0208-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0527-x"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.01.015"},{"key":"e_1_2_11_42_1","unstructured":"Patterson C.(2018).World Alzheimer report 2018: the state of the art of dementia research: new frontiers. Alzheimer\u2019s Disease International (ADI): London UK."},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14142"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2011.04.012"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0703627"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2005-7203"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0501-8"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt362"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e3181b76415"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-019-04426-0"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww214"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0380-x"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.26.041002.131412"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.3.270"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199708000-00011"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00162-J"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0731584.x"},{"key":"e_1_2_11_58_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/ana.410300410","article-title":"Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment","volume":"30","author":"Terry R. D.","year":"1991","journal-title":"Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1791"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010131"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.5.378"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.1290080510"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.09.046"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15487","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.15487","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15487","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T05:05:12Z","timestamp":1693285512000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,2]]},"references-count":62,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/jnc.15487"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15487","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,2]]},"assertion":[{"value":"2020-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}