Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
Neurol Sci. 2023 Sep;44(9):3287-3290. doi: 10.1007/s10072-023-06882-x. Epub 2023 Jun 7.
Alzheimer's disease (AD) is characterized by decreased cerebrospinal fluid (CSF) Aβ42 and Aβ42/Aβ40 ratio. Aβ peptides can now be measured also in plasma and are promising peripheral biomarkers for AD. We evaluated the relationships of plasma Aβ species with their CSF counterparts, kidney function, and serum/CSF albumin ratio (Q-Alb) in AD patients.
We measured plasma Aβ42 and Aβ40, as well as CSF AD biomarkers, with the fully automated Lumipulse platform in a cohort of N = 30 patients with clinical and neurochemical diagnosis of AD.
The two plasma Aβ peptides correlated strongly with each other (r = 0.7449), as did the corresponding CSF biomarkers (r = 0.7670). On the contrary, the positive correlations of plasma Aβ42, Aβ40, and Aβ42/Aβ40 ratio with their CSF counterparts and the negative correlation of plasma Aβ42/Aβ40 ratio with CSF P-tau181 were not statistically significant. Plasma levels of both Aβ species negatively correlated with estimated glomerular filtration rate (eGFR) (Aβ42: r = -0.4138; Aβ40: r = -0.6015), but plasma Aβ42/Aβ40 ratio did not. Q-Alb did not correlate with any plasma Aβ parameter.
Plasma Aβ42 and Aβ40 are critically influenced by kidney function; however, their ratio is advantageously spared from this effect. The lack of significant correlations between plasma Aβ species and their CSF counterparts is probably mainly due to small sample size and inclusion of only Aβ + individuals. Q-Alb is not a major determinant of plasma Aβ concentrations, highlighting the uncertainties about mechanisms of Aβ transfer between CNS and periphery.
阿尔茨海默病(AD)的特征是脑脊液(CSF)中 Aβ42 和 Aβ42/Aβ40 比值降低。现在也可以在血浆中测量 Aβ 肽,并且是 AD 的有前途的外周生物标志物。我们评估了 AD 患者血浆 Aβ 种类与其 CSF 对应物、肾功能和血清/CSF 白蛋白比值(Q-Alb)之间的关系。
我们使用全自动 Lumipulse 平台测量了 30 名具有 AD 临床和神经化学诊断的患者的血浆 Aβ42 和 Aβ40 以及 CSF AD 生物标志物。
两种血浆 Aβ 肽彼此之间呈强相关(r=0.7449),相应的 CSF 生物标志物也是如此(r=0.7670)。相反,血浆 Aβ42、Aβ40 和 Aβ42/Aβ40 比值与 CSF 对应物的正相关以及与 CSF P-tau181 的负相关在统计学上均不显著。两种 Aβ 物质的血浆水平与估计肾小球滤过率(eGFR)呈负相关(Aβ42:r=-0.4138;Aβ40:r=-0.6015),但 Aβ42/Aβ40 比值无相关性。Q-Alb 与任何血浆 Aβ 参数均无相关性。
血浆 Aβ42 和 Aβ40 受肾功能的严重影响;然而,其比值不受此影响。血浆 Aβ 种类与其 CSF 对应物之间缺乏显著相关性,这可能主要是由于样本量小且仅包括 Aβ+个体。Q-Alb 不是血浆 Aβ 浓度的主要决定因素,这突出了关于 CNS 和外周之间 Aβ 转移机制的不确定性。