脑脊液 N-224tau 有助于区分阿尔茨海默病与主观认知下降和其他痴呆症。
Cerebrospinal fluid N-224 tau helps discriminate Alzheimer's disease from subjective cognitive decline and other dementias.
机构信息
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
出版信息
Alzheimers Res Ther. 2021 Feb 8;13(1):38. doi: 10.1186/s13195-020-00756-6.
BACKGROUND
Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer's disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls.
METHODS
Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (Aβ42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay.
RESULTS
N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson's disease (PD, p < 0.0001), Parkinson's disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R = 0.318, β = 0.564, p ≤ 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824).
CONCLUSIONS
N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.
背景
脑脊液（CSF）中总 tau（T-tau）和磷酸化 tau 蛋白在 Thr181 位（P-tau181）的浓度升高是阿尔茨海默病（AD）的典型特征。然而，T-tau 检测仅测量蛋白的中部区域，而 CSF 中的 tau 实际上由一系列片段组成。特别是一种片段物质 N-224，在 AD 患者中与对照组相比水平升高。在这项多中心研究中，我们在包括有主观认知下降（SCD）、轻度认知障碍（MCI）、AD、非 AD 痴呆和对照组的队列中对 N-224 检测进行了临床验证。
方法
队列包括来自阿姆斯特丹痴呆队列（队列 1）的 30 名 SCD 和 30 名可能的 AD 患者，以及来自瑞典生物发现者研究（队列 2）的 539 名对照者、195 名 SCD、232 名 MCI、137 名 AD 和 253 名非 AD 患者。所有样本均进行了 AD 核心生物标志物（Aβ42、T-tau、P-tau181）测量。N-224 使用内部超灵敏 Simoa 检测进行测量。
结果
AD 患者的 N-224 水平明显高于 SCD（队列 1：p=0.003），且在队列 2 中，AD 患者的 N-224 水平明显高于所有其他诊断组（对照组、SCD、MCI 和非 AD，p<0.0001）。在非 AD 组中，与 AD 相比，帕金森病（PD，p<0.0001）、帕金森病痴呆（PDD，p=0.004）、进行性核上性麻痹（PSP，<0.0001）、多系统萎缩（MSA，p=0.002）和帕金森病非特定类型（NOS，p=0.007）的 N-224 浓度明显较低。在队列 1 中，较高的 N-224 浓度与较低的 Mini-Mental State Examination（MMSE）评分相关（R=0.318，β=0.564，p≤0.0001），并能准确识别病理性（<24）MMSE 评分（p<0.0001，AUC=0.824）。
结论
N-224 tau 可区分 AD 患者与 SCD，可区分非 AD 痴呆与 AD。因此，N-224 可能是 CSF 中 tau 标志物工具箱的有用补充，有助于研究 CSF 中的 tau 物质，并更好地了解疾病发病机制。
Zotero 插件