Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.
G. H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.
JAMA Netw Open. 2023 Apr 3;6(4):e238214. doi: 10.1001/jamanetworkopen.2023.8214.
Cerebrospinal fluid (CSF) and plasma biomarkers can detect biological evidence of Alzheimer disease (AD), but their use in low-resource environments and among minority ethnic groups is limited.
To assess validated plasma biomarkers for AD among adults of Caribbean Hispanic ethnicity.
DESIGN, SETTING, AND PARTICIPANTS: In this decision analytical modeling study, adults were recruited between January 1, 2018, and April 30, 2022, and underwent detailed clinical assessments and venipuncture. A subsample of participants also consented to lumbar puncture. Established CSF cut points were used to define AD biomarker-positive status, allowing determination of optimal cut points for plasma biomarkers in the same individuals. The performance of a panel of 6 plasma biomarkers was then assessed with respect to the entire group. Data analysis was performed in January 2023.
Main outcomes were the association of plasma biomarkers amyloid-β 1-42 (Aβ42), amyloid-β 1-40 (Aβ40), total tau (T-tau), phosphorylated tau181 (P-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) with AD diagnosis. These biomarkers allow assessment of amyloid (A), neurofibrillary degeneration (T), and neurodegeneration (N) aspects of AD. Statistical analyses performed included receiver operating characteristics, Pearson and Spearman correlations, t tests, and Wilcoxon rank-sum, chi-square, and Fisher exact tests.
Exposures included age, sex, education, country of residence, apolipoprotein-ε4 (APOE-ε4) allele number, serum creatinine, blood urea nitrogen, and body mass index.
This study included 746 adults. Participants had a mean (SD) age of 71.0 (7.8) years, 480 (64.3%) were women, and 154 (20.6%) met clinical criteria for AD. Associations were observed between CSF and plasma P-tau181 (r = .47 [95% CI, 0.32-0.60]), NfL (r = 0.57 [95% CI, 0.44-0.68]), and P-tau181/Aβ42 (r = 0.44 [95% CI, 0.29-0.58]). For AD defined by CSF biomarkers, plasma P-tau181 and P-tau181/Aβ42 provided biological evidence of AD. Among individuals judged to be clinically healthy without dementia, biomarker-positive status was determined by plasma P-tau181 for 133 (22.7%) and by plasma P-tau181/Aβ42 for 104 (17.7%). Among individuals with clinically diagnosed AD, 69 (45.4%) had plasma P-tau181 levels and 89 (58.9%) had P-tau181/Aβ42 levels that were inconsistent with AD. Individuals with biomarker-negative clinical AD status tended to have lower levels of education, were less likely to carry APOE-ε4 alleles, and had lower levels of GFAP and NfL than individuals with biomarker-positive clinical AD.
In this cross-sectional study, plasma P-tau181 and P-tau181/Aβ42 measurements correctly classified Caribbean Hispanic individuals with and without AD. However, plasma biomarkers identified individuals without dementia with biological evidence of AD, and a portion of those with dementia whose AD biomarker profile was negative. These results suggest that plasma biomarkers can augment detection of preclinical AD among asymptomatic individuals and improve the specificity of AD diagnosis.
脑脊液 (CSF) 和血浆生物标志物可检测阿尔茨海默病 (AD) 的生物学证据，但它们在资源有限的环境中和少数族裔群体中的使用受到限制。
评估加勒比西班牙裔成年人中 AD 的经验证的血浆生物标志物。
设计、地点和参与者：在这项决策分析建模研究中，参与者于 2018 年 1 月 1 日至 2022 年 4 月 30 日期间招募，并接受详细的临床评估和静脉穿刺。部分参与者也同意进行腰椎穿刺。使用既定的 CSF 切点来定义 AD 生物标志物阳性状态，从而确定同一人群中血浆生物标志物的最佳切点。然后评估了一组 6 种血浆生物标志物在整个组中的性能。数据分析于 2023 年 1 月进行。
主要结果是血浆生物标志物β淀粉样蛋白 1-42 (Aβ42)、β淀粉样蛋白 1-40 (Aβ40)、总tau (T-tau)、磷酸化 tau181 (P-tau181)、神经胶质纤维酸性蛋白 (GFAP) 和神经丝轻链 (NfL) 与 AD 诊断的关联。这些生物标志物允许评估 AD 的淀粉样蛋白 (A)、神经纤维变性 (T) 和神经退行性变 (N) 方面。进行的统计分析包括接收者操作特征、Pearson 和 Spearman 相关性、t 检验和 Wilcoxon 秩和、卡方和 Fisher 精确检验。
暴露包括年龄、性别、教育、居住国家、载脂蛋白 E4 (APOE-ε4) 等位基因数量、血清肌酐、血尿素氮和体重指数。
这项研究包括 746 名成年人。参与者的平均 (SD) 年龄为 71.0±7.8 岁，480 名 (64.3%) 为女性，154 名 (20.6%) 符合 AD 的临床标准。CSF 和血浆 P-tau181 (r=0.47 [95% CI, 0.32-0.60])、NfL (r=0.57 [95% CI, 0.44-0.68]) 和 P-tau181/Aβ42 (r=0.44 [95% CI, 0.29-0.58]) 之间存在相关性。对于通过 CSF 生物标志物定义的 AD，血浆 P-tau181 和 P-tau181/Aβ42 提供了 AD 的生物学证据。在被判断为无痴呆的临床健康个体中，血浆 P-tau181 确定了 133 名 (22.7%) 的生物标志物阳性状态，而血浆 P-tau181/Aβ42 确定了 104 名 (17.7%) 的生物标志物阳性状态。在临床诊断为 AD 的个体中，69 名 (45.4%) 有血浆 P-tau181 水平，89 名 (58.9%) 有 P-tau181/Aβ42 水平与 AD 不一致。具有阴性临床 AD 状态的个体往往受教育程度较低，携带 APOE-ε4 等位基因的可能性较低，GFAP 和 NfL 水平也低于具有阳性临床 AD 状态的个体。
在这项横断面研究中，血浆 P-tau181 和 P-tau181/Aβ42 测量正确分类了有和没有 AD 的加勒比西班牙裔个体。然而，血浆生物标志物在无症状个体中识别出具有 AD 生物学证据的个体，并在一部分具有 AD 生物标志物阴性的痴呆个体中识别出具有 AD 生物学证据的个体。这些结果表明，血浆生物标志物可以增加无症状个体的 AD 前检测，并提高 AD 诊断的特异性。
