{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:05:56Z","timestamp":1791655556866,"version":"4.3.4"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyloidosis refers to a clinically heterogeneous group of disorders characterized by the extracellular deposition of amyloid proteins in various tissues of the body. To date, 42 different amyloid proteins that originate from normal precursor proteins and are associated with distinct clinical forms of amyloidosis have been described. Identification of the amyloid type is essential in clinical practice, since prognosis and treatment regimens both vary according to the particular amyloid disease. However, typing of amyloid protein is often challenging, especially in the two most common forms of amyloidosis, i.e., the immunoglobulin light chain amyloidosis and transthyretin amyloidosis. Diagnostic methodology is based on tissue examinations as well as on noninvasive techniques including serological and imaging studies. Tissue examinations vary depending on the tissue preparation mode, i.e., whether it is fresh-frozen or fixed, and they can be carried out by ample methodologies including immunohistochemistry, immunofluorescence, immunoelectron microscopy, Western blotting, and proteomic analysis. In this review, we summarize current methodological approaches used for the diagnosis of amyloidosis and discusses their utility, advantages, and limitations. Special attention is paid to the simplicity of the procedures and their availability in clinical diagnostic laboratories. Finally, we describe new methods recently developed by our team to overcome limitations existing in the standard assays used in common practice.<\/jats:p>","DOI":"10.3390\/ijms24054655","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:00:38Z","timestamp":1677553238000},"page":"4655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Diagnostic Challenges and Solutions in Systemic Amyloidosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Rivka","family":"Goldis","sequence":"first","affiliation":[{"name":"Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-681X","authenticated-orcid":false,"given":"Batia","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Institute of Hematology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga (Lesya)","family":"Kukuy","sequence":"additional","affiliation":[{"name":"Institute of Nephrology and Hypertension, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Arad","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Heart Failure Institute, Leviev Heart Centre, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-394X","authenticated-orcid":false,"given":"Hila","family":"Magen","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Multiple Myeloma Unit, Hematology Department, Sheba Medical Center, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efrat","family":"Shavit-Stein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-1481","authenticated-orcid":false,"given":"Amir","family":"Dori","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Livneh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sheba Medical Center, Tel Hashomer, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/13506129.2022.2147636","article-title":"Amyloid nomenclature 2022: Update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee","volume":"29","author":"Buxbaum","year":"2022","journal-title":"Amyloid"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0889-8588(18)30347-2","article-title":"Mechanisms of disease\u2014Monoclonal immunoglobulin deposition\u2014Amyloidosis, light chain deposition disease, and light and heavy-chain deposition disease","volume":"6","author":"Buxbaum","year":"1992","journal-title":"Hematol. 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