Gómez-Tortosa Estrella, Agüero-Rabes Pablo, Ruiz-González Alicia, Wagner Sonia, Téllez Raquel, Mahillo Ignacio, Ruiz-Calvo Andrea, Sainz María José, Nystrom Anna Lena, Cremades-Jimeno Lucía, Del Ser Teodoro, Sánchez-Juan Pascual
Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain.
Instituto de Investigación Sanitaria, Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.
Aging Dis. 2024 Nov 6. doi: 10.14336/AD.2024.1260.
Plasma biomarkers represent promising tools for the screening and diagnosis of patients with neurodegenerative conditions. However, it is crucial to account for the effects of aging on biomarker profiles, especially in the oldest segments of the population. Additionally, biomarkers in this sample can offer in vivo insights into the physiological mechanisms underlying brain aging while concomitantly supporting cognitive preservation. In this study we analyzed plasma Alzheimer's disease (AD) core biomarkers, neurofilament light chain (NfL), and glial fibrillary acid protein (GFAP) using the Single Molecule Array (SIMOA) platform in 75 cognitively preserved nonagenarians, and compared with baseline samples of 153 volunteers who were cognitively unimpaired (CU) during six years (classified in ≤ 70, and 71 to 85 years of age), and with 108 AD patients. Nonagenarians almost lack the APOEε4 allele, and had significantly higher Aß40, Aß42, p-tau181, NfL, and GFAP, along with a significantly lower Aß42/40 ratio (P&;lt0.001) compared with the two CU groups. NfL and GFAP tripled concentrations in nonagenarians. No differences were noted in any plasma biomarker between the younger and older CU groups. Biomarkers correlated strongly with age only when analyzing together CU controls and nonagenarians. Compared with AD cases, nonagenarians showed lower p-tau181 (P=0.001), higher total tau (P=0.02), and much higher Aß40, Aß42 and NfL levels (P&;lt0.001). The levels of GFAP in nonagenarians were similar to those observed in AD patients. In conclusion, cognitively preserved nonagenarians do not develop the AD biomarker signature and exhibit higher levels of Aß42. However, their threefold increase in NfL and GFAP supports their aging brains are somehow resilient to neurodegeneration. These data support caution in the prognosis of clinical dementia based on NfL and GFAP values. Overall, plasma biomarkers in CU individuals remained quite stable till the eighties.
血浆生物标志物是筛查和诊断神经退行性疾病患者的有前景的工具。然而，考虑衰老对生物标志物谱的影响至关重要，尤其是在老年人群体中。此外，该样本中的生物标志物可以提供关于大脑衰老潜在生理机制的体内见解，同时支持认知保护。在本研究中，我们使用单分子阵列（SIMOA）平台分析了75名认知功能保留的九旬老人的血浆阿尔茨海默病（AD）核心生物标志物、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP），并与153名在六年中认知未受损（CU）的志愿者（分为≤70岁以及71至85岁）的基线样本，以及108名AD患者进行了比较。九旬老人几乎缺乏APOEε4等位基因，与两个CU组相比，他们的Aβ40、Aβ42、p-tau181、NfL和GFAP显著更高，而Aβ42/40比值显著更低（P＜0.001）。九旬老人中NfL和GFAP的浓度增加了两倍。在年轻和年长的CU组之间，任何血浆生物标志物均未观察到差异。仅在将CU对照者和九旬老人一起分析时，生物标志物才与年龄密切相关。与AD病例相比，九旬老人的p-tau181更低（P = 0.001），总tau更高（P = 0.02），Aβ40、Aβ42和NfL水平更高得多（P＜0.001）。九旬老人中GFAP的水平与AD患者中观察到的水平相似。总之，认知功能保留的九旬老人未出现AD生物标志物特征，且Aβ42水平更高。然而，他们的NfL和GFAP增加两倍表明其衰老的大脑在某种程度上对神经退行性变具有弹性。这些数据支持在基于NfL和GFAP值进行临床痴呆预后判断时要谨慎。总体而言，CU个体的血浆生物标志物直到八十岁都保持相当稳定。
