Biomarkers identified for diagnosing AD in patients with Down syndrome
medwireNews: Plasma neurofilament light protein (NfL) concentrations and cerebrospinal fluid (CSF) biomarkers are effective for diagnosing Alzheimer’s disease (AD) in patients with Down syndrome, say researchers.
“The most clinically relevant finding was the excellent diagnostic performance of plasma NfL”, note Juan Fortea (Hospital of Sant Pau, Barcelona, Spain) and co-researchers, adding that the findings “consequently support the use of plasma NfL as an easily accessible biomarker for the early detection of [AD] in individuals with Down syndrome as part of clinical routine.”
Indeed, at levels of 14.2 pg/mL or above NfL distinguished between 54 Down syndrome individuals without symptoms of AD and 22 with AD dementia with a sensitivity of 90% and a specificity of 92%.
“Therefore, plasma NfL could aid in the clinical diagnosis of cognitive impairment in people with Down syndrome, which is far more complex than in the general population, because it requires the demonstration of deterioration in a population with a pre-existing intellectual disability,” the team highlights in The Lancet Neurology.
NfL was the only plasma biomarker that distinguished the 194 Down syndrome patients without AD from the 39 with prodromal AD and the 49 with AD dementia, with an area under the curve (AUC) of 0.88 and 0.95, respectively, in receiver operating characteristic analysis. The diagnostic performance of plasma biomarkers was otherwise poor (AUC between 0.53 and 0.74).
Fortea and colleagues also found CSF biomarkers, measured in 94 of the participants with Down syndrome, of whom 54 were asymptomatic, 18 had prodromal AD and 22 had AD dementia, were effective for diagnosing AD. Comparing asymptomatic patients with those with prodromal AD, the AUC was 0.60 for CSF amyloid β (Aβ)1–40, 0.92 for CSF Aβ1–42, 0.81 for t-tau, 0.80 for p-tau, and 0.88 for CSF NfL. The respective AUCs for distinguishing between asymptomatic patients and those with AD dementia were 0.59, 0.92, 0.93, 0.90 and 0.98.
The optimal sensitivity and specificity for differentiating asymptomatic Down syndrome patients from those with AD dementia was a respective 100% and 76% for Aβ1–42 at a cutoff of 508.8 pg/mL, 86% and 92% for t-tau at a cutoff of 472.5 pg/mL and 100% and 87% for CSF NfL at a cutoff of 624.6 pg/mL.
The researchers note that “NfL showed the optimal diagnostic performance and was the only biomarker to show a robust plasma–CSF correlation.”
In a related commentary, Michael Rafii (University of Southern California, San Diego, USA) says that the findings support “the notion that individuals with Down syndrome experience virtually the same pathological process in later life as individuals with sporadic [AD].”
He concludes: “The finding that biomarkers, including NfL concentrations, have superior diagnostic performance in Down syndrome compared with the general population reminds us that this group, which is genetically enriched for [AD], continues to be an important population to study, much as it [was]nearly 35 years ago.”
By Lucy Piper
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