Prognostic performance and longitudinal changes in plasma Neurofilament light levels in adults with Down syndrome: a multicentre longitudinal study

Maria Carmona-Iragui, Daniel Alcolea, Isabel Barroeta, Laura Videla, Laia Muñoz, Kathryn Van Pelt, Frederick Schmitt, Donita Lightner, Lisa Koehl, Gregory Jicha, Silvia Sacco, Clotilde Mircher, Sarah Pape, Rosalyn Hithersay, Isabel Clare, Anthony Holland, Georg Nübling, Johannes Levin, Shahid Zaman, Andre StrydomAnne-Sophie Rebillat, Elizabeth Head, Rafael Blesa, Alberto Lleó, Juan Fortea

Research output: Contribution to journalArticlepeer-review


We sought to validate the clinical utility of plasma Neurofilament light (NfL), its prognostic value, and the longitudinal changes in a multicentre cohort of adults with Down syndrome.
We included adults with Down syndrome with longitudinal follow-up and at least two plasma samples from six centres. Participants were classified as asymptomatic, prodromal Alzheimer’s disease, or Alzheimer’s disease dementia, blind to biomarker data. We classified as “Progressors” those individuals that progressed along the Alzheimer’s continuum during the follow up. Plasma NfL levels were measured using commercial kits for the Simoa SR-XTM. We performed ANOVA to evaluate differences in baseline NfL levels, Cox regression to study their prognostic value, and linear mixed models to estimate longitudinal changes.
We analysed 572 samples from 226 participants with Down syndrome (165 asymptomatic (70%), 32 prodromal Alzheimer’s (14%), and 29 Alzheimer’s dementia (12%)). Mean follow-up was 3·6 (SD 1·6) years. Baseline plasma NfL levels showed an area under the ROC curve of 0·83 (95%CI 0·76-0·91) and 0·94 (95%CI 0·90-0·97) in differentiating asymptomatic participants from those in the prodromal and dementia groups, respectively. An increase in 1pg/ml in baseline NfL levels was associated to 1·04-fold risk of clinical progression (95%CI 1·02-1·07). Plasma NfL adjusted levels remained stable in non-progressors, but they showed an annual increase of 2·3 pg/ml (0·8-3·9) in the group of asymptomatic progressors, 3·3 pg/ml (1·6-4·9) in prodromal Alzheimer’s disease progressors, and 6·5 pg/ml (3·2-9·8 pg/ml) in participants with Alzheimer’s disease dementia.
Plasma NfL levels have excellent diagnostic and prognostic performance for the diagnosis of symptomatic Alzheimer in Down syndrome. The longitudinal trajectory of plasma NfL enables its use as a theragnostic marker in clinical trials.
Original languageEnglish
JournalThe Lancet Neurology
Publication statusAccepted/In press - 16 Apr 2021


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