The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: A decade of discovery

Abstract

Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) that offers crucial insights into AD pathogenesis. The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) is a population-based multimodal biomarker cohort studying AD's natural history and clinical trials in DS. DABNI included 1135 participants (mean age 42.82, 46.3% female). At baseline, 673 participants were cognitively stable, 113 had prodromal AD, 239 had AD dementia, and 110 were uncertain due to non-AD conditions. Over 10 years, > 10000 clinical visits were conducted; follow-up showed that progression to symptomatic AD before age 40 was rare, but rates increased after age 50 (> 50% within 5 years). Neuropsychological and biomarker assessments demonstrated excellent diagnostic performance and a predictable sequence of changes, similar to autosomal dominant AD. DABNI participates in AD clinical trials and produced approximately 100 publications. The 10-year DABNI study provided critical insights into DS-associated AD (DSAD) and serves as a key platform for DS clinical trials. HIGHLIGHTS: Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) is a population-based multimodal cohort studying Alzheimer's disease in Down syndrome. Over 10 years, 1135 participants contributed to more than 10000 clinical visits and extensive biomarker studies. DABNI findings have transformed the understanding of Alzheimer's disease in Down syndrome, reinforcing its classification as a genetic form of the disease. The cohort integrates clinical care and research, enhancing early detection and patient management. DABNI supports clinical trials and has produced over 100 publications advancing Down syndrome-related Alzheimer's research.

Keywords: Alzheimer's disease; DABNI; Down syndrome; autosomal dominant Alzheimer's disease; biomarkers; clinical trials; cognition; health.

FIGURE 1

DABNI flowchart. The health plan run at the Alzheimer‐down Unit and the biomarker cohort, are integrated to optimize data collection and the participant pathway. CSF, cerebrospinal fluid; DABNI, Down Alzheimer Barcelona Neuroimaging Initiative; EEG, electroencephalogram; MRI, magnetic resonance imaging.

FIGURE 2

DABNI participants in different clinical and research assessments. The volunteers in the pictures have signed their consent to appear in them and have given permission for their dissemination. DABNI, Down Alzheimer Barcelona Neuroimaging Initiative.

FIGURE 3

DABNI's chronogram including milestones and contributions to DSAD. ABATE, autoimmunity‐blocking antibody for tolerance; AD, Alzheimer's disease; ADAD, autosomal dominant Alzheimer's disease; APOE, apolipoprotein E; βCTF, 𝛽‐C‐terminal fragment; BF, basal forebrain; CAA, cerebral amyloid angiopathy; CSF, cerebrospinal fluid; GFAP, glial fibrillary acidic protein; DABNI, Down Alzheimer Barcelona Neuroimaging Initiative; DAVIS: domiciliary Alzheimer visiting in Down syndrome; DS, Down syndrome; DSAD, Down syndrome Alzheimer's disease; FCSD, Fundació Catalana Síndrome de Down; HSP, Hospital de Sant Pau; HFO, hight frequency oscillations; ID, intellectual disability; NGF, nerve growth factor; NfL, neurofilament light polypeptide; NPTX2, CPAP, continuous positive airway pressure; neuronal pentraxin 2; OSA, obstructive sleep apnea; PET, positron emission tomography; REM, rapid eye movement; SAD, sporadic Alzheimer's disease; TRC‐DS, Trial Ready Cohort – Down syndrome; WMH, white matter hyperintensities.