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However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt,\u00a0A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charit\u00e9 Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was\u00a0more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS\u2009\u2265\u200920. We therefore conclude that\u00a0highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.<\/jats:p>","DOI":"10.1038\/s41598-024-60025-6","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T08:02:33Z","timestamp":1714636953000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8711-5526","authenticated-orcid":false,"given":"Helena F.","family":"Pernice","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-0394","authenticated-orcid":false,"given":"Adrian L.","family":"Knorz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9393-5512","authenticated-orcid":false,"given":"Paul J.","family":"Wetzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2384-7303","authenticated-orcid":false,"given":"Carolin","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harisa","family":"Muratovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7833-2272","authenticated-orcid":false,"given":"Finn","family":"Rieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2677-3266","authenticated-orcid":false,"given":"Eleonora","family":"Asaad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Fi\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-2159","authenticated-orcid":false,"given":"Gina","family":"Barzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-8795","authenticated-orcid":false,"given":"Elisabeth","family":"Bl\u00fcthner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2095-6806","authenticated-orcid":false,"given":"Fabian","family":"Knebel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-8007","authenticated-orcid":false,"given":"Sebastian","family":"Spethmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Messroghli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3811-7920","authenticated-orcid":false,"given":"Bettina","family":"Heidecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-1375","authenticated-orcid":false,"given":"Christoph","family":"Wetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5243-8985","authenticated-orcid":false,"given":"Carsten","family":"Tsch\u00f6pe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6013-0072","authenticated-orcid":false,"given":"Katrin","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"60025_CR1","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1016\/j.medcle.2020.06.033","volume":"73","author":"FL Ruberg","year":"2019","unstructured":"Ruberg, F. 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HP also received personal funding by Deutsche Gesellschaft f\u00fcr Muskelkranke (DGM) GmbH. Adrian Knorz, Gunnar Fi\u00df, Harisa Muratovic, Paul Wetzel, Finn Rieber, Carolin Herrmann and Eleonora Asaad declare they have no conflict of interest. Katrin Hahn received financial reimbursement for consulting, advisory board activities, speaker fees and\/or contributions to congresses and travel support to attend scientific meetings by Akcea Therapeuticals Inc., Alnylam Pharmaceuticals Inc., Amicus, AstraZeneca, GSK, Hormosan, Takeda Pharmaceutical Inc., Pfizer Pharmaceuticals Inc., Swedish Orphan Biovitrum Inc and ViiV Healthcare GmbH. KH further received research funding by the foundation Charit\u00e9 (BIH clinical fellow), Alnylam Pharmaceuticals \ufeffInc., and Pfizer Pharmaceuticals. Fabian Knebel received speaker honoraria from Alnylam Inc., Pfizer Inc., and research support from Alnylam Inc and Pfizer Inc. Christoph Wetz received a speaker honorarium from Company Novartis, Pfizer and Alnylam Pharmaceuticals; and received grants\/research support from Novartis. Bettina Heidecker has received speaker fees and research funding from Pfizer Pharmaceuticals Inc., AstraZeneca, and Boehringer Ingelheim unrelated to this project. \ufeffFabian Knebel received speaker honoraria from Alnylam Inc., Pfizer Inc., and research support from Alnylam Inc and Pfizer Inc. Sebastian Spethmann received financial reimbursement for lectures from Pfizer Pharmaceuticals. Elisabeth Bl\u00fcthner received consultation, lecture, advisory board honoraria and grant research support from Takeda Pharmaceuticals Inc. Anna Brand received a speaker honorarium from Pfizer. Daniel Messroghli has received honoraria for speaking at symposia from Pfizer, Alnylam and Akcea and research funding from Pfizer. Carsten Tsch\u00f6pe has received speaker fees and\/or contributions to congresses from Abbott, Abiomed, Astra Zeneca, Bayer, Novartis, Pfizer, and Servier; all outside the submitted work. Gina Barzen received personal funding by Alnylam Pharmaceuticals Inc.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10111"}}