NDEV levels of Aβ40, Aβ42, Tau, pTauT181, pTauT231, NfL, and SNAP25 were significantly higher in people with DS diagnosed with compared to those with no cognitive decline.
Individuals with Down syndrome (DS) show an ultra-high risk of developing (AD).
Plasma samples from 33 individuals with DS and AD dementia, 31 with prodromal AD, and 43 with no cognitive decline were analyzed.
Higher levels of neuron-derived extracellular vesicle (NDEV) biomarkers were observed in middle-aged or older women compared to males.
The increase in NDEV biomarkers may indicate the onset of Alzheimer's disease in individuals with DS.
Simplified
INTRODUCTION: Individuals with Down syndrome (DS) are at an ultra-high risk of developing (AD). Diagnosis of AD onset in people with DS can be challenging due to the variable degrees of intellectual disability and cognitive impairment among individuals.
METHODS: Plasma samples from individuals with DS diagnosed with AD dementia (n = 33), (n = 31), or cognitively stable (n = 43) were enriched for (NDEV) using immunocapture with the L1CAM antibody. We used single-molecule array technology to quantify amyloid-β (Aβ) peptides, Tau, phosphorylated Tau, neurofilament light chain (NfL), and synaptosomal-associated protein 25 (SNAP25) across diagnostic groups.
RESULTS: NDEV levels of Aβ40, Aβ42, Tau, pTauT181, pTauT231, NfL, and SNAP25 were significantly higher in people with DS diagnosed with prodromal AD compared to those with no cognitive decline. Middle-aged or older women had higher levels of NDEV biomarkers compared to males.
DISCUSSION: NDEV biomarker levels can inform on the onset of AD in individuals with DS.
HIGHLIGHTS: Diagnosis of Alzheimer's dementia in individuals with Down syndrome (DS)is challenging. Neuron-derived extracellular vesicles were enriched from plasma of adults with Down syndrome. Alzheimer's disease biomarkers were measured using single molecule array technology. NDEV biomarkers accurately predicted the prodromal stage of dementia in people with DS.
Key numbers
317%
Increase in NDEV Biomarkers
Comparison of NDEV levels between and cognitively stable individuals with DS.
0.96
Predictive AUC for Onset
Backward stepwise logistic regression model including age and NDEV biomarkers.
107
Sample Size
Total number of participants across different diagnostic groups.
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J.F. reported receiving personal fees for service on the advisory boards, adjudication committees or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Novo Nordisk, Perha, Roche, Zambón and outside the submitted work. J.F. reports holding a patent for markers of synaptopathy in neurodegenerative disease (licensed to ADx, EPI8382175.0). M.C.I. reports receiving personal fees for service on the advisory boards, speaker honoraria or educational activities from Esteve, Lilly, Neuraxpharm, Adium and Roche diagnostics. D.A. participated in advisory boards from Fujirebio‐Europe, Roche Diagnostics, Grifols S.A. and Lilly, and received speaker honoraria from Fujirebio‐Europe, Roche Diagnostics, Nutricia, Krka Farmacéutica S.L., Zambon S.A.U., Neuraxpharm, Alter Medica, Lilly and Esteve Pharmaceuticals S.A. D.A. declares a filed patent application (WO2019175379 A1 Markers of synaptopathy in neurodegenerative disease). Al.L. reported receiving consulting fees from Eisai, Esteve, Fujirebio‐Europe, Roche, Grifols S.A. and Lilly. A.L, B.B. and L.V. do not have anything to disclose. Author disclosures are available in the Supporting Information.
