Neurofilament Light Biomarkers Identify Alzheimer Disease Risk in Down Syndrome

Lumbar Puncture procedure
Lumbar Puncture procedure
Investigators analyzed the diagnostic performance of plasma cerebrospinal fluid and neurofilament light biomarkers in patients with Down syndrome and Alzheimer disease.

Plasma cerebrospinal fluid (CSF) and neurofilament light (NfL) biomarkers offer good diagnostic performance for detecting Alzheimer disease (AD) in patients with Down syndrome, according to a study in Lancet Neurology.

Between February 1, 2013 and November 30, 2017, a multi-international team of researchers recruited participants with Down syndrome using a population from the Down Alzheimer Barcelona Neuroimaging Initiative that was linked to a population­based health plan in Spain (N=282). Participants were asymptomatic (n=194) or had prodromal AD (n=39) or AD dementia (n=49). A subset of patients with a plasma or CSF sample available for analysis were also recruited (n=94). A total of 67 nontrisomic control participants were also enrolled as a convenience sample.

Study investigators performed neurologic and neuropsychologic examinations and blood sampling, and lumbar puncture was performed in a subset of participants. In addition, the researchers quantified plasma amyloid-β (Aβ)1-40, Aβ1-42, total tau (t-tau), 181-phosphorylated tau (p-tau [only in CSF]), and NfL concentrations in CSF. Control participants were compared with patients with Down syndrome with regard to plasma and CSF biomarker concentrations. In addition, the diagnostic performance of plasma NfL and CSF biomarkers were compared between asymptomatic participants and patients with prodromal AD and between asymptomatic participants and patients with AD dementia.

According to receiver operating characteristic curve analyses, the diagnostic performance of Aβ1-40, Aβ1-42, and t­tau for asymptomatic individuals vs participants with prodromal AD was poor (Aβ1-40: area under the curve [AUC] 0.65 [95% CI, 0.56-0.74]; Aβ1-42: AUC 0.53 [95% CI, 0.44-0.62]; and t­tau: AUC 0.74 [95% CI, 0.66-0.82). The diagnostic capability of plasma NfL concentrations, however, was high for the differentiation of asymptomatic individuals vs prodromal AD participants (AUC 0.88 [95% CI, 0.82-0.93]) and vs the AD dementia group (AUC 0.95 [95% CI, 0.92-0.98]).

In the asymptomatic vs prodromal AD comparison analysis, good diagnostic performance was observed for Aβ1-42 (AUC 0.92 [95% CI, 0.85-0.99]), t-tau (AUC 0.81 [95% CI, 0.69-0.94]), p-tau (AUC 0.80 [95% CI, 0.67-0.93), and NfL (AUC 0.88 [95% CI, 0.79-0.96]) biomarkers. The NfL biomarker demonstrated the strongest association between plasma Aβ1-40 and CSF biomarker concentrations in patients with Down syndrome (P <.0001).

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The researchers noted the use of cross-sectional data for the assessment of changes in plasma NfL concentrations as the study’s main limitation.

Assessment of plasma NfL concentrations may “be of value in clinical routine and in clinical trials as an easily accessible biomarker of early AD­related neurodegeneration in Down syndrome,” the researchers concluded.


Fortea J, Carmona-Iragui M, Benejam B, et al. Plasma and CSF biomarkers for the diagnosis of Alzheimer’s disease in adults with Down syndrome: a cross-sectional study. Lancet Neurol. 2018;17(10):860-869.