{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:42:53Z","timestamp":1776318173736,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging","award":["1T ZIAAct AG000455"],"award-info":[{"award-number":["1T ZIAAct AG000455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>(1) Background and aims: Amyloidosis due to aggregation of amyloid-\u03b2 (A\u03b242) is a key pathogenic event in Alzheimer\u2019s disease (AD), whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islets leads to \u03b2-cell dysfunction. The aim of this study is to uncover potential biomarkers that might additionally point to therapy for early AD patients. (2) Methods: We used bioinformatic approach to uncover novel IAPP isoforms and developed a quantitative selective reaction monitoring (SRM) proteomic assay to measure their peptide levels in human plasma and CSF from individuals with early AD and controls, as well as postmortem cerebrum of clinical confirmed AD and controls. We used Thioflavin T amyloid reporter assay to measure the IAPP isoform fibrillation propensity and anti-amyloid potential against aggregation of A\u03b242 and IAPP37. (3) Results: We uncovered hominid-specific IAPP isoforms: hIAPP\u03b2, which encodes an elongated propeptide, and hIAPP\u03b3, which is processed to mature IAPP25 instead of IAPP37. We found that hIAPP\u03b2 was significantly reduced in the plasma of AD patients with the accuracy of 89%. We uncovered that IAPP25 and a GDNF derived DNSP11 were nonaggregating peptides that inhibited the aggregation of IAPP37 and A\u03b242. (4) Conclusions: The novel peptides derived from hIAPP isoforms have potential to serve as blood-derived biomarkers for early AD and be developed as peptide based anti-amyloid medicine.<\/jats:p>","DOI":"10.3390\/biom13010167","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T05:09:32Z","timestamp":1673586572000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel Hominid-Specific IAPP Isoforms: Potential Biomarkers of Early Alzheimer\u2019s Disease and Inhibitors of Amyloid Formation"],"prefix":"10.3390","volume":"13","author":[{"given":"Qing-Rong","family":"Liu","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Investigation, NIA-NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, NIA-NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4464-564X","authenticated-orcid":false,"given":"Qinghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, NIA-NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-2047","authenticated-orcid":false,"given":"Maja","family":"Mustapic","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, NIA-NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2181-3118","authenticated-orcid":false,"given":"Dimitrios","family":"Kapogiannis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, NIA-NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephine M.","family":"Egan","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, NIA-NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R121","DOI":"10.1530\/JME-17-0105","article-title":"The beta-cell assassin: IAPP cytotoxicity","volume":"59","author":"Raleigh","year":"2017","journal-title":"J. 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