Busto Germain U, Hirtz Christophe, Carriere Isabelle, Bennys Karim, Gutierrez Laure-Anne, Kindermans Jana, Helmer Catherine, Gabelle Audrey, Lehmann Sylvain, Berr Claudine
INM, University of Montpellier, INSERM, 80 Av. Augustin Fliche, 34000, Montpellier, France; Memory Resource and Research Center, Department of Neurology, University of Montpellier Hospital, 80 avenue Augustin Fliche, 34295, Montpellier, France.
INM, University of Montpellier, INSERM, 80 Av. Augustin Fliche, 34000, Montpellier, France; University of Montpellier, IRMB, CHU Montpellier, 80 avenue Augustin Fliche, 34295, Montpellier, France.
J Prev Alzheimers Dis. 2025 Aug;12(7):100186. doi: 10.1016/j.tjpad.2025.100186. Epub 2025 Apr 19.
Identifying individuals at risk for dementia and Alzheimer's disease (AD) in the general population (GP) is increasingly essential due to new diagnostic criteria and opportunities for effective interventions. Plasma-based biomarkers (pBB) offer a promising approach for detecting positive amyloid profile. However, their effectiveness in predicting clinical dementia and AD risk at the GP level remains largely unexplored.
To assess the risk of clinical dementia and AD using pBB amyloid biomarkers in GP using the most up-to-date proteomic techniques.
Case-cohort study randomly selected from a prospective cohort.
The three-city community-living study.
Over 65 years recruited from the electoral rolls of three French cities.
pBB amyloid levels (Aβ42, Aβ40 and APP669-711) were measured in the plasma using the mass spectrometry-based (IPMS)-Shimadzu modified technology. Patients were monitored for up to 6 years for incident dementia and AD according to DSM-IV and NINCDS/ADRDA criteria. Cox proportional hazard models adjusted for multiple covariables, including age and renal function, were used to estimate hazard ratios.
Plasma samples from 327 participants were analyzed with a mean age 83 years (80-87), 64.8 % females and a median follow-up time of 2.7 years (0.8-4.8) and including 121 incident dementia cases. Our findings indicate that the Aβ42/Aβ40 ratio, along with a composite score that encompasses APP669-711 and Aβ40/Aβ42 ratios, serves as significant predictors of clinical dementia [HR(95 %CI) = 3.52 (1.69-7.32), p-value<0.001 and 4.34 (2.06-9.17), p-value<0.001, respectively] and AD risk over a six-year period, while also accounting for age and sex interactions. Furthermore, elevated Aβ40 levels correlate with an increased risk of developing dementia (HR=2.56, 95 % CI 1.22-5.35, p = 0.01) and AD (HR=2.60, 95 %CI 1.06-6.36, p = 0.04), and our study confirms that Aβ42 concentrations are significantly influenced by renal function.
This research advances the potential application of plasma amyloid biomarkers for assessing the risk of clinical dementia and AD in the general population within short period of time, positioning it as a valuable tool alongside existing plasma PT217 biomarkers or using ratio of both of them.
由于新的诊断标准以及有效干预措施的出现，在普通人群中识别痴呆症和阿尔茨海默病（AD）的风险个体变得越来越重要。基于血浆的生物标志物（pBB）为检测阳性淀粉样蛋白谱提供了一种有前景的方法。然而，它们在预测普通人群临床痴呆和AD风险方面的有效性在很大程度上仍未得到探索。
使用最新的蛋白质组学技术，评估基于pBB淀粉样蛋白生物标志物的普通人群临床痴呆和AD风险。
从前瞻性队列中随机选取的病例对照研究。
三城市社区生活研究。
从法国三个城市的选民名单中招募的65岁以上人群。
使用基于质谱的（IPMS）-岛津改良技术测量血浆中的pBB淀粉样蛋白水平（Aβ42、Aβ40和APP669 - 711）。根据DSM - IV和NINCDS/ADRDA标准，对患者进行长达6年的痴呆症和AD发病监测。使用调整了包括年龄和肾功能在内的多个协变量的Cox比例风险模型来估计风险比。
对327名参与者的血浆样本进行了分析，平均年龄83岁（80 - 87岁），女性占64.8%，中位随访时间为2.7年（0.8 - 4.8年），包括121例痴呆症发病病例。我们的研究结果表明，Aβ�2/Aβ40比值以及包含APP669 - 711和Aβ40/Aβ42比值的综合评分，是临床痴呆症[风险比（95%置信区间）= 3.52（1.69 - 7.32），p值<0.001和4.34（2.06 - 9.17），p值<0.001，分别]和六年内AD风险的显著预测指标，同时也考虑了年龄和性别相互作用。此外，Aβ40水平升高与痴呆症发病风险增加（风险比= 2.56，95%置信区间1.22 - 5.35，p = 0.01）和AD（风险比= 2.60，95%置信区间1.06 - 6.36，p = 0.04）相关，并且我们的研究证实Aβ42浓度受肾功能显著影响。
本研究推进了血浆淀粉样蛋白生物标志物在短时间内评估普通人群临床痴呆和AD风险的潜在应用，使其成为与现有血浆PT217生物标志物或两者比值并列的有价值工具。
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