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We obtained multiple monoclonal antibody (mAb) clones that were reactive against hIAPP protofibrils. A secondary screen was carried out to identify clones that cross\u2010reacted with amyloid beta\u2010peptide (A\u03b242) protofibrils, but not with A\u03b240 monomers. These mAbs were further characterized in several in vitro assays, in immunohistological studies of a mouse model of Alzheimer's disease (AD) and in AD patient brain tissue. We show that mAbs obtained by immunizing mice with the NUCB1\u2010hIAPP complex cross\u2010react with A\u03b242, specifically targeting protofibrils and inhibiting their further aggregation. In line with conformation\u2010specific binding, the mAbs appear to react with an intracellular antigen in diseased tissue, but not with amyloid plaques. We hypothesize that the mAbs we describe here recognize a secondary or quaternary structural epitope that is common to multiple amyloid protofibrils. In summary, we report a method to create mAbs that are conformation\u2010sensitive and sequence\u2010independent and can target more than one type of protofibril species.<\/jats:p>","DOI":"10.1111\/jcmm.14119","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T07:16:10Z","timestamp":1548054970000},"page":"2103-2114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Conformation\u2010specific antibodies against multiple amyloid protofibril species from a single amyloid immunogen"],"prefix":"10.1111","volume":"23","author":[{"given":"Alessandra","family":"Bonito\u2010Oliva","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Biology &amp; Signal Transduction The Rockefeller University New York City New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Schedin\u2010Weiss","sequence":"additional","affiliation":[{"name":"Division of 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