Influence of kidney function and CSF/serum albumin ratio on plasma Aβ42 and Aβ40 levels measured on a fully automated platform in patients with Alzheimer's disease.

Abstract

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.