Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
van der Ende Emma L, Xiao Meifang, Xu Desheng, Poos Jackie M, Panman Jessica L, Jiskoot Lize C, Meeter Lieke H, Dopper Elise Gp, Papma Janne M, Heller Carolin, Convery Rhian, Moore Katrina, Bocchetta Martina, Neason Mollie, Peakman Georgia, Cash David M, Teunissen Charlotte E, Graff Caroline, Synofzik Matthis, Moreno Fermin, Finger Elizabeth, Sánchez-Valle Raquel, Vandenberghe Rik, Laforce Robert, Masellis Mario, Tartaglia Maria Carmela, Rowe James B, Butler Christopher R, Ducharme Simon, Gerhard Alex, Danek Adrian, Levin Johannes, Pijnenburg Yolande Al, Otto Markus, Borroni Barbara, Tagliavini Fabrizio, de Mendonca Alexandre, Santana Isabel, Galimberti Daniela, Seelaar Harro, Rohrer Jonathan D, Worley Paul F, van Swieten John C, Genetic Frontotemporal Dementia Initiative (GENFI)
Аннотация
METHODS: We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses.
RESULTS: Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage.
DISCUSSION: We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.