Ledreux Aurélie, Carmona-Iragui Maria, Videla Laura, Benejam Bessy, Barroeta Isabel, Lleó Alberto, Alcolea Daniel, Fortea Juan
Department of Neurosurgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Alzheimers Dement. 2025 Jun;21(6):e70380. doi: 10.1002/alz.70380.
Individuals with Down syndrome (DS) are at an ultra-high risk of developing Alzheimer's disease (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.
Plasma samples from individuals with DS diagnosed with AD dementia (n = 33), prodromal AD (n = 31), or cognitively stable (n = 43) were enriched for neuron-derived extracellular vesicles (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.
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.
NDEV biomarker levels can inform on the onset of AD in individuals with DS.
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.
唐氏综合征（DS）患者患阿尔茨海默病（AD）的风险极高。由于DS患者的智力残疾和认知障碍程度各不相同，因此诊断其AD发病具有挑战性。
使用L1CAM抗体免疫捕获技术，从被诊断为AD痴呆（n = 33）、前驱AD（n = 31）或认知稳定（n = 43）的DS患者血浆样本中富集神经元衍生的细胞外囊泡（NDEV）。我们使用单分子阵列技术对各诊断组中的淀粉样β（Aβ）肽、 Tau、磷酸化Tau、神经丝轻链（NfL）和突触体相关蛋白25（SNAP25）进行定量。
与无认知衰退的DS患者相比，被诊断为前驱AD的DS患者的NDEV中Aβ40、Aβ42、Tau、pTauT181、pTauT231、NfL和SNAP25水平显著更高。与男性相比，中年或老年女性的NDEV生物标志物水平更高。
NDEV生物标志物水平可为DS患者AD的发病提供信息。
唐氏综合征（DS）患者的阿尔茨海默病痴呆诊断具有挑战性。从唐氏综合征成人血浆中富集神经元衍生的细胞外囊泡。使用单分子阵列技术测量阿尔茨海默病生物标志物。NDEV生物标志物准确预测了DS患者痴呆的前驱阶段。
