Hendrix James A, Airey David C, Britton Angela, Burke Anna D, Capone George T, Chavez Ronelyn, Chen Jacqueline, Chicoine Brian, Costa Alberto C S, Dage Jeffrey L, Doran Eric, Esbensen Anna, Evans Casey L, Faber Kelley M, Foroud Tatiana M, Hart Sarah, Haugen Kelsey, Head Elizabeth, Hendrix Suzanne, Hillerstrom Hampus, Kishnani Priya S, Krell Kavita, Ledesma Duvia Lara, Lai Florence, Lott Ira, Ochoa-Lubinoff Cesar, Mason Jennifer, Nicodemus-Johnson Jessie, Proctor Nicholas Kyle, Pulsifer Margaret B, Revta Carolyn, Rosas H Diana, Rosser Tracie C, Santoro Stephanie, Schafer Kim, Scheidemantel Thomas, Schmitt Frederick, Skotko Brian G, Stasko Melissa R, Talboy Amy, Torres Amy, Wilmes Kristi, Woodward Jason, Zimmer Jennifer A, Feldman Howard H, Mobley William
LuMind IDSC, 20 Mall Road, Suite 200, Burlington, MA 01803-4126, USA.
Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA.
J Clin Med. 2021 Apr 28;10(9):1907. doi: 10.3390/jcm10091907.
With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ, Aβ), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.
随着医疗保健水平的提高，唐氏综合征（DS）患者群体数量不断增加且老龄化迅速。然而，随着寿命延长，患阿尔茨海默病（AD）的风险非常高。LIFE-DSR研究（NCT04149197）是一项纵向自然史研究，招募了270名25岁以上的成年DS患者。该研究旨在描述与DS相关的AD（DS-AD）的变化轨迹。本研究报告了对首批入组的90名受试者的横断面分析。采用先前发表的方法检测血浆生物标志物磷酸化tau蛋白（p-tau）、神经丝轻链（NfL）、淀粉样β肽（Aβ）和胶质纤维酸性蛋白（GFAP）。基线访视的临床数据包括人口统计学信息以及严重损伤量表（SIB）和唐氏综合征精神状态检查（DS-MSE）下的认知测量。描述了生物标志物分布，并观察到与参与者年龄有很强的统计关联。生物标志物数据有助于理解疾病全谱中的DS-AD。总体而言，生物标志物数据显示DS-AD进展的证据始于大约40岁。在整个LIFE-DSR纵向研究人群中探索这些数据将是理解DS-AD病理生理学的发病、进展和临床特征的重要资源。
