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We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Comparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)\u2013(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in<jats:italic>C9orf72<\/jats:italic>,<jats:italic>GRN<\/jats:italic>or<jats:italic>MAPT<\/jats:italic>; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg\/mL) in Bland-Altman analysis: 1.12\u00b11.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2023-332464","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T05:35:13Z","timestamp":1705901713000},"page":"822-828","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI 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