Longitudinal plasma levels of neurofilament light in Down syndrome: A multicenter study: Biomarkers (non‐neuroimaging) / Longitudinal change over time. (7th December 2020)

• Record Type: Journal Article
• Authors: Alcolea, Daniel; Carmona‐Iragui, Maria; Barroeta, Isabel; Videla, Laura; Muñoz, Laia; Van Pelt, Kathryn L; Schmitt, Frederick A; Lightner, Donita; Koehl, Lisa; Sacco, Silvia; Mircher, Clotilde; Pape, Sarah; Nübling, Georg; Levin, Johannes; Zaman, Shahid; Strydom, Andre; Rebillat, Anne‐Sophie; Head, Elizabeth; Blesa, Rafael; Lleó, Alberto; Fortea, Juan
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.044772
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Plasma Neurofilament light (NfL) has been proposed as a useful biomarker to detect Alzheimer's disease dementia in Down syndrome. To validate its clinical utility and implement it in clinical trials, it is essential to understand the longitudinal changes of this biomarker, and the association of these changes to clinical progression. Method: We included participants with Down syndrome evaluated in six different centers. All participants provided at least two plasma samples and were clinically classified as asymptomatic (aDS), prodromal Alzheimer's disease (pDS) or Alzheimer's disease dementia (dDS). The aDS and pDS participants were subsequently classified as "Progressors" when their diagnosis changed to pDS or dDS, respectively, at any time throughout follow up visits. Plasma NfL levels were measured using commercially available kits for the Simoa SR‐X TM (Quanterix). We performed ANCOVA and Cox regression to evaluate group differences in baseline NfL levels and their association with prognosis. We used linear mixed models to estimate longitudinal trajectories of plasma NfL in all groups. Result: We analyzed 575 samples from 226 participants classified as aDS (n=165), pDS (n=32) or dDS (n=29). Participants in the pDS and dDS groups were older than aDS (50.6 and 53.3 vs. 38.9, respectively; p<0.001). After adjusting for age, sex and intellectual disability, levels of NfL were 79.9% higher (p<0.001) in dDS and 40.5% higher (p<0.001) in pDS compared to aDS (Figure 1). The highest tertile of baseline plasma NfL was associated to a 5.9 fold risk of clinical progression (p<0.001; Figure 2). Longitudinally, aDS non‐progressors showed an annual increase of 2.7% (0.2%‐5.3%, p=0.036) in NfL levels, significantly different from 12.2% (5.1%‐19.9%, p=0.014) in aDS progressors, 16.1% (8.7%‐24%, p=0.001) in pDS progressors and 21.7% (13.2%‐30.9%, p<0.001) in dDS (Figure 3). Conclusion: This study confirms the clinical utility of plasma NfL to diagnose symptomatic Alzheimer in Down syndrome, but also shows that the annual increase in NfL levels do not plateau in dementia stages. These longitudinal trajectories enable its use as a theragnostic marker in clinical trials.