在两个记忆门诊队列中 CSF p-tau235 与 p-tau181、p-tau217 和 p-tau231 的临床性能和头对头比较。
Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts.
机构信息
Department of Psychiatry & Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Institut national de la santé et de la recherche médicale U1144 Optimisation Thérapeutique en Neuropsychopharmacologie, Université de Paris, Paris, France.
出版信息
Alzheimers Res Ther. 2023 Mar 10;15(1):48. doi: 10.1186/s13195-023-01201-0.
BACKGROUND
Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer's disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully reflect the patient landscape found in clinical settings. Therefore, in this multicentre study, we investigated the performance of CSF p-tau235 to detect symptomatic AD in clinical settings and compared it with CSF p-tau181, p-tau217 and p-tau231.
METHODS
CSF p-tau235 was measured using an in-house single molecule array (Simoa) assay in two independent memory clinic cohorts: Paris cohort (Lariboisière Fernand-Widal University Hospital Paris, France; n=212) and BIODEGMAR cohort (Hospital del Mar, Barcelona, Spain; n=175). Patients were classified by the syndromic diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI] or dementia) and their biological diagnosis (amyloid-beta [Aβ]+ or Aβ -). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF Aβ ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231).
RESULTS
High CSF p-tau235 levels were strongly associated with CSF amyloidosis regardless of the clinical diagnosis, being significantly increased in MCI Aβ+ and dementia Aβ+ when compared with all other Aβ- groups (Paris cohort: P ˂0.0001 for all; BIODEGMAR cohort: P ˂0.05 for all). CSF p-tau235 was pronouncedly increased in the A+T+ profile group compared with A-T- and A+T- groups (P ˂0.0001 for all). Moreover, CSF p-tau235 demonstrated high diagnostic accuracies identifying CSF amyloidosis in symptomatic cases (AUCs=0.86 to 0.96) and discriminating AT groups (AUCs=0.79 to 0.98). Overall, CSF p-tau235 showed similar performances to CSF p-tau181 and CSF p-tau231 when discriminating CSF amyloidosis in various scenarios, but lower than CSF p-tau217. Finally, CSF p-tau235 associated with global cognition and memory domain in both cohorts.
CONCLUSIONS
CSF p-tau235 was increased with the presence of CSF amyloidosis in two independent memory clinic cohorts. CSF p-tau235 accurately identified AD in both MCI and dementia patients. Overall, the diagnostic performance of CSF p-tau235 was comparable to that of other CSF p-tau measurements, indicating its suitability to support a biomarker-based AD diagnosis in clinical settings.
背景
脑脊液（CSF）中的 p-tau235 是一种新型生物标志物，对阿尔茨海默病（AD）具有高度特异性。然而，CSF p-tau235 仅在特征明确的研究队列中进行了研究，这些队列不能完全反映临床环境中发现的患者情况。因此，在这项多中心研究中，我们研究了 CSF p-tau235 在临床环境中检测有症状 AD 的性能，并将其与 CSF p-tau181、p-tau217 和 p-tau231 进行了比较。
方法
使用内部单分子阵列（Simoa）测定法在两个独立的记忆诊所队列中测量 CSF p-tau235：巴黎队列（法国巴黎 Lariboisière Fernand-Widal 大学医院；n=212）和 BIODEGMAR 队列（西班牙巴塞罗那 Hospital del Mar；n=175）。根据综合征诊断（认知正常[CU]、轻度认知障碍[MCI]或痴呆）和生物诊断（淀粉样蛋白-β [Aβ]+或 Aβ-）对患者进行分类。两个队列均进行了详细的认知评估和 CSF 生物标志物测量（临床验证的核心 AD 生物标志物[Lumipulse CSF Aβ 比值、p-tau181 和 t-tau]和内部开发的 Simoa CSF p-tau181、p-tau217 和 p-tau231）。
结果
高 CSF p-tau235 水平与 CSF 淀粉样蛋白沉积密切相关，无论临床诊断如何，MCI Aβ+和痴呆 Aβ+患者的 CSF p-tau235 水平均显著升高，与所有其他 Aβ-组相比（巴黎队列：所有 P ˂0.0001；BIODEGMAR 队列：所有 P ˂0.05）。与 A-T-和 A+T-组相比，A+T+ 谱组的 CSF p-tau235 明显升高（所有 P ˂0.0001）。此外，CSF p-tau235 具有较高的诊断准确性，可识别有症状病例中的 CSF 淀粉样蛋白沉积（AUCs=0.86 至 0.96）和区分 AT 组（AUCs=0.79 至 0.98）。总体而言，CSF p-tau235 在各种情况下区分 CSF 淀粉样蛋白沉积时，与 CSF p-tau181 和 CSF p-tau231 的表现相似，但低于 CSF p-tau217。最后，CSF p-tau235 在两个队列中均与整体认知和记忆域相关。
结论
在两个独立的记忆诊所队列中，CSF p-tau235 在存在 CSF 淀粉样蛋白沉积时增加。CSF p-tau235 可准确识别 MCI 和痴呆患者中的 AD。总体而言，CSF p-tau235 的诊断性能与其他 CSF p-tau 测量相当，表明其适合在临床环境中支持基于生物标志物的 AD 诊断。
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