{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:42:11Z","timestamp":1790991731409,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>This study was undertaken to assess skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv\u2010PN), a treatable disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this single center retrospective study, skin Congo red staining and intraepidermal nerve fiber density (IENFD) were evaluated in symptomatic ATTRv\u2010PN patients and asymptomatic <jats:italic>TTR<\/jats:italic> gene mutation carriers between 2012 and 2019. Non\u2010ATTRv subjects with suspected small fiber neuropathy who underwent skin biopsy during the same timespan were used as controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred eighty\u2010three symptomatic ATTRv\u2010PN patients, 36 asymptomatic carriers, and 537 non\u2010ATTRv patients were included. Skin biopsy demonstrated amyloid depositions in 80% of the 183 symptomatic cases. Skin amyloid deposits were found in 75% of early stage ATTRv\u2010PN patients, and in 14% of asymptomatic carriers. All 183 symptomatic and 34 of 36 asymptomatic patients displayed decreased ankle IENFD with a proximal\u2013distal gradient distribution, and reduced IEFND correlated with disease severity and duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrates skin amyloid deposits are a marker of ATTRv\u2010PN disease onset, and decreased IENFD a marker of disease progression. These results are of major importance for the early identification of ATTRv\u2010PN patients in need of disease\u2010modifying treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15268","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T18:22:56Z","timestamp":1643653376000},"page":"1477-1487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1267-864X","authenticated-orcid":false,"given":"Luca","family":"Leonardi","sequence":"first","affiliation":[{"name":"Referral Center for Familial Amyloid Polyneuropathy and Other Rare Peripheral Neuropathies and Department of Neurology Bic\u00eatre University Hospital Public Hospital Network of Paris  Le Kremlin Bic\u00eatre 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