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Longitudinal plasma levels of neurofilament light in Down syndrome: A multicenter study
Author(s) -
Alcolea Daniel,
CarmonaIragui 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 AnneSophie,
Head Elizabeth,
Blesa Rafael,
Lleó Alberto,
Fortea Juan
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044772
Subject(s) - biomarker , medicine , asymptomatic , dementia , down syndrome , disease , oncology , psychology , psychiatry , biochemistry , chemistry
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.