Cerebrospinal fluid biomarkers of Alzheimer's disease in a cohort of adults with Down syndrome
Cerebrospinal fluid biomarkers of Alzheimer's disease in a cohort of adults with Down syndrome
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DOI：
10.1002/dad2.12057
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发表时间：
2020-01-01
影响因子：
5.3
通讯作者：
Fagan, Anne M.
中科院分区：
文献类型：
--
作者：
Henson, Rachel L.;Doran, Eric;Fagan, Anne M.
几乎所有唐氏综合症（DS）患者在40岁时都会发展为阿尔茨海默病（AD）。脑脊液（CSF）生物标志物表征了迟发性AD （LOAD）和常染色体显性AD （ADAD）队列中的AD病理。很少有研究评估成年退行性椎体滑移患者的这些生物标志物。方法检测来自阿尔茨海默病生物标志物联盟-陶氏综合征研究的44例成人DS患者脑脊液中淀粉样蛋白β (A β)40、β 42、tau、磷酸化-tau181 （p-tau）、神经丝轻链（NfL）、髓样细胞表达的可溶性触发受体2 （sTREM2）、几丁质酶-3样蛋白1 （YKL-40）、α突触核蛋白（α Syn）、神经粒蛋白（Ng）、突触体相关蛋白25 （SNAP-25）和视蛋白样蛋白1 （VILIP-1）的scsf浓度。通过认知状态、年龄和载脂蛋白E基因（APOE） epsilon 4携带者状态评估生物标志物水平。结果淀粉样蛋白沉积、牛头病、神经变性、突触功能障碍和神经炎症等生物标志物异常与认知障碍增加有关。年龄和APOE epsilon 4状态影响一些生物标志物。在成人退行性痴呆队列中，许多已建立和新出现的AD脑脊液生物标志物的特征与LOAD和ADAD中报道的相似，但也观察到一些差异。
IntroductionVirtually all individuals with Down syndrome (DS) will develop Alzheimer's disease (AD) pathology by age 40. Cerebrospinal fluid (CSF) biomarkers have characterized AD pathology in cohorts of late-onset AD (LOAD) and autosomal-dominant AD (ADAD). Few studies have evaluated such biomarkers in adults with DS.MethodsCSF concentrations of amyloid beta (A beta)40, A beta 42, tau, phospho-tau181 (p-tau), neurofilament light chain (NfL), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase-3-like protein 1 (YKL-40), alpha synuclein (alpha Syn), neurogranin (Ng), synaptosomal-associated protein 25 (SNAP-25), and visinin-like protein 1 (VILIP-1) were assessed in CSF from 44 adults with DS from the Alzheimer's Biomarker Consortium-Down Syndrome study. Biomarker levels were evaluated by cognitive status, age, and apolipoprotein E gene (APOE) epsilon 4 carrier status.ResultsBiomarker abnormalities indicative of amyloid deposition, tauopathy, neurodegeneration, synaptic dysfunction, and neuroinflammation were associated with increased cognitive impairment. Age and APOE epsilon 4 status influenced some biomarkers.DiscussionThe profile of many established and emerging CSF biomarkers of AD in a cohort of adults with DS was similar to that reported in LOAD and ADAD, while some differences were observed.