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stiftelse","award":["2020-O000028"],"award-info":[{"award-number":["2020-O000028"]}]},{"name":"S\u00f6derbergs stiftelse","award":["2022-1259"],"award-info":[{"award-number":["2022-1259"]}]},{"name":"S\u00f6derbergs stiftelse","award":["2022-1259"],"award-info":[{"award-number":["2022-1259"]}]},{"name":"S\u00f6derbergs stiftelse","award":["M55\/22"],"award-info":[{"award-number":["M55\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreas-derived islet amyloid polypeptide (IAPP) crosses the blood\u2013brain barrier and co-deposits with amyloid beta (A\u03b2) in brains of type 2 diabetes (T2D) and Alzheimer\u2019s disease (AD) patients. Depositions might be related to the circulating IAPP levels, but it warrants further investigation. Autoantibodies recognizing toxic IAPP oligomers (IAPPO) but not monomers (IAPPM) or fibrils have been found in T2D, but studies on AD are lacking. In this study, we have analyzed plasma from two cohorts and found that levels of neither immunoglobulin (Ig) M, nor IgG or IgA against IAPPM or IAPPO were altered in AD patients compared with controls. However, our results show significantly lower IAPPO-IgA levels in apolipoprotein E (APOE) 4 carriers compared with non-carriers in an allele dose-dependent manner, and the decrease is linked to the AD pathology. Furthermore, plasma IAPP-Ig levels, especially IAPP-IgA, correlated with cognitive decline, C-reactive protein, cerebrospinal fluid A\u03b2 and tau, neurofibrillary tangles, and brain IAPP exclusively in APOE4 non-carriers. We speculate that the reduction in IAPPO-IgA levels may be caused by increased plasma IAPPO levels or masked epitopes in APOE4 carriers and propose that IgA and APOE4 status play a specific role in clearance of circulatory IAPPO, which may influence the amount of IAPP deposition in the AD brain.<\/jats:p>","DOI":"10.3390\/ijms24043776","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T02:41:56Z","timestamp":1676342516000},"page":"3776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Plasma IAPP-Autoantibody Levels in Alzheimer\u2019s Disease Patients Are Affected by APOE4 Status"],"prefix":"10.3390","volume":"24","author":[{"given":"Dovil\u0117","family":"Pocevi\u010di\u016bt\u0117","sequence":"first","affiliation":[{"name":"Cognitive Disorder Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 214 28 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Lund University, Sk\u00e5ne University Hospital, 214 28 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-6455","authenticated-orcid":false,"given":"Nina","family":"Schultz","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 223 62 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Nu\u00f1ez-Diaz","sequence":"additional","affiliation":[{"name":"Cognitive Disorder Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 214 28 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 223 62 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Netherlands Brain Bank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8743-8720","authenticated-orcid":false,"given":"Anders","family":"Olofsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 223 62 Lund, Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital, 212 24 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Wennstr\u00f6m","sequence":"additional","affiliation":[{"name":"Cognitive Disorder Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, 214 28 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.1073\/pnas.83.13.4913","article-title":"Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology","volume":"83","author":"Iqbal","year":"1986","journal-title":"Proc. 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