University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France.
Resource and Research Memory Center (CMRR), Department of Neurology, Montpellier University Hospital, 80 avenue Augustin Fliche, 34000, Montpellier, France.
Alzheimers Res Ther. 2023 Feb 18;15(1):34. doi: 10.1186/s13195-023-01188-8.
Alzheimer's disease (AD) is a complex neurodegenerative disorder with β-amyloid pathology as a key underlying process. The relevance of cerebrospinal fluid (CSF) and brain imaging biomarkers is validated in clinical practice for early diagnosis. Yet, their cost and perceived invasiveness are a limitation for large-scale implementation. Based on positive amyloid profiles, blood-based biomarkers should allow to detect people at risk for AD and to monitor patients under therapeutics strategies. Thanks to the recent development of innovative proteomic tools, the sensibility and specificity of blood biomarkers have been considerably improved. However, their diagnosis and prognosis relevance for daily clinical practice is still incomplete.
The Plasmaboost study included 184 participants from the Montpellier's hospital NeuroCognition Biobank with AD (n = 73), mild cognitive impairments (MCI) (n = 32), subjective cognitive impairments (SCI) (n = 12), other neurodegenerative diseases (NDD) (n = 31), and other neurological disorders (OND) (n = 36). Dosage of β-amyloid biomarkers was performed on plasma samples using immunoprecipitation-mass spectrometry (IPMS) developed by Shimadzu (IPMS-Shim Aβ, Aβ, APP) and Simoa Human Neurology 3-PLEX A assay (Aβ, Aβ, t-tau). Links between those biomarkers and demographical and clinical data and CSF AD biomarkers were investigated. Performances of the two technologies to discriminate clinically or biologically based (using the AT(N) framework) diagnosis of AD were compared using receiver operating characteristic (ROC) analyses.
The amyloid IPMS-Shim composite biomarker (combining APP/Aβ and Aβ/Aβ ratios) discriminated AD from SCI (AUC: 0.91), OND (0.89), and NDD (0.81). The IPMS-Shim Aβ ratio also discriminated AD from MCI (0.78). IPMS-Shim biomarkers have similar relevance to discriminate between amyloid-positive and amyloid-negative individuals (0.73 and 0.76 respectively) and A-T-N-/A+T+N+ profiles (0.83 and 0.85). Performances of the Simoa 3-PLEX Aβ ratio were more modest. Pilot longitudinal analysis on the progression of plasma biomarkers indicates that IPMS-Shim can detect the decrease in plasma Aβ that is specific to AD patients.
Our study confirms the potential usefulness of amyloid plasma biomarkers, especially the IPMS-Shim technology, as a screening tool for early AD patients.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，β-淀粉样蛋白病理学是其关键的潜在过程。脑脊液（CSF）和脑成像生物标志物在临床实践中的相关性已得到验证，可用于早期诊断。然而，其成本和被认为的侵入性是大规模实施的限制因素。基于阳性淀粉样蛋白谱，基于血液的生物标志物应该可以检测到 AD 风险人群，并监测治疗策略下的患者。由于创新性蛋白质组学工具的最新发展，血液生物标志物的敏感性和特异性得到了极大的提高。然而，它们在日常临床实践中的诊断和预后相关性仍不完整。
Plasmaboost 研究纳入了来自蒙彼利埃医院神经认知生物库的 184 名参与者，包括 AD 患者（n = 73）、轻度认知障碍（MCI）患者（n = 32）、主观认知障碍（SCI）患者（n = 12）、其他神经退行性疾病（NDD）患者（n = 31）和其他神经疾病（OND）患者（n = 36）。使用岛津公司（IPMS-Shim Aβ、Aβ、APP）和 Simoa Human Neurology 3-PLEX A 测定法（Aβ、Aβ、t-tau）对血浆样本中的 β-淀粉样蛋白生物标志物进行定量。研究了这些生物标志物与人口统计学和临床数据以及 CSF AD 生物标志物之间的关系。使用接收者操作特征（ROC）分析比较了两种技术来区分临床或基于生物学的（使用 AT(N) 框架）AD 诊断。
淀粉样蛋白 IPMS-Shim 复合生物标志物（组合了 APP/Aβ 和 Aβ/Aβ 比值）可将 AD 与 SCI（AUC：0.91）、OND（0.89）和 NDD（0.81）区分开来。IPMS-Shim Aβ 比值也可将 AD 与 MCI 区分开来（0.78）。IPMS-Shim 生物标志物在区分淀粉样蛋白阳性和阴性个体方面具有相似的相关性（分别为 0.73 和 0.76），以及 A-T-N-/A+T+N+ 谱（0.83 和 0.85）。Simoa 3-PLEX Aβ 比值的性能更为温和。对血浆生物标志物进展的初步纵向分析表明，IPMS-Shim 可以检测到 AD 患者特异性的血浆 Aβ 下降。
我们的研究证实了淀粉样蛋白血浆生物标志物的潜在用途，尤其是 IPMS-Shim 技术，作为早期 AD 患者的筛查工具。
