Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Patients with Alzheimer's Disease and Other Dementias: A Center-Based Study

Abstract

Neuropsychological interviews and neuroimaging techniques are traditional diagnostic methods for Alzheimer's disease (AD). However, the development of blood-based biomarkers, such as Amyloid beta (Aβ), phosphorylated Tau (pTau), and their ratios, offers promising non-invasive alternatives for early AD detection. This study aimed to analyze the correlation between CSF and plasma biomarkers (Aβ40, Aβ42, Aβ42/Aβ40, pTau181) and evaluate their diagnostic performance in 51 patients with cognitive impairments. Biomarkers were analyzed in both plasma and CSF using an automated chemiluminescence enzyme immunoassay, Lumipulse (Fujirebio). The results showed significant positive correlations between CSF and plasma levels of Aβ42, the Aβ42/Aβ40 ratio, and pTau181, but not for Aβ40. Plasma Aβ42, pTau181, Aβ42/Aβ40 ratio, and pTau181/Aβ42 ratio demonstrated significant differences between patients A+ vs. A- classified based on CSF Amyloid status, as well as between those classified as A+T+ and A-T- according to both CSF Amyloid and Tau levels. Plasma pTau181, Aβ42/Aβ40, and pTau181/Aβ42 ratio showed high diagnostic accuracy in distinguishing A+ from A- (AUC = 0.93-0.95) and A+T+ from A-T- patients (AUC = 0.93-0.97). These findings suggest that plasma biomarkers can effectively differentiate between AD and other forms of dementia, and serve as a reliable, non-invasive tool for early detection and monitoring of Alzheimer's disease.

Keywords: Alzheimer’s disease; CSF; amyloid β (Aβ); hyperphosphorylated tau (pTau); mild cognitive and vascular impairment; plasma.

Figure 1

Aβ42, Aβ40, Aβ42/Aβ40, and pTau181: correlation between plasma and CSF. The diagrams represent (a) Aβ42 concentrations, (b) Aβ40 concentrations, (c) Aβ42/Aβ40 ratios, (d) pTau181 concentrations in CSF and plasma. The values expressed as pg/mL, except for Aβ42/Aβ40 ratio. Outliers: one for plasma Aβ42/Aβ40 (0.135), two for plasma pT181 (11.32 pg/mL, 5.05 pg/mL), and one for CSF pT181 (>400 pg/mL) were excluded from the analysis to enhance the accuracy of the conclusion. The symbols represent the CSF and plasma concentration of a single sample, with the colors corresponding to CSF AT status (green A+T−, blue A+T+, red A−T−). Abbreviations: Aβ, Amyloid beta; pTau181, tau protein phosphorylated at residue 181; CSF, cerebrospinal fluid.

Figure 2

Plasma biomarkers value in A+ and A− groups. The graphs represent the box and whiskers plots of (a) Aβ42 concentrations, (b) Aβ42/Aβ40 ratios, (c) pTau181 concentrations, and (d) pTau181/Aβ42 ratio. All values are expressed in pg/mL, with the exception of the Aβ42/Aβ40 and pTau181/Aβ42 ratios. Each point corresponds to an individual value. Statistical significance was determined using a Student’s t-test for Aβ42 concentrations and Aβ42/Aβ40 ratios and the Mann–Whitney test for pTau181 concentrations and the pTau181/Aβ42 ratio. Abbreviations: Aβ, Amyloid beta; pTau181, tau protein phosphorylated at residue 181; A−, Amyloid negative; A+, Amyloid positive.

Figure 3

Plasma biomarkers value according to CSF status. The graphs represent the box and whiskers plots of (a) Aβ42 concentrations, (b) Aβ42/Aβ40 ratios, (c) pTau181 concentrations, and (d) pT181/Aβ42 ratios. All values are expressed in pg/mL, with the exception of the Aβ42/Aβ40 and pTau181/Aβ42 ratios. Each point corresponds to an individual value. Significant differences were assessed using a Kruskal–Wallis test followed by Steel–Dwass–Critchlow–Fligner test: n = 23, A+T+; n = 21, A−T−; n = 5, A+T−. Abbreviations: Aβ, Amyloid beta; pTau181, tau protein phosphorylated at residue 181; A−, Amyloid negative; A+, Amyloid positive; T−, tau negative, T+, tau positive.

Figure 4

Plasma biomarkers value according to clinical diagnosis status. The graphs represent the box and whiskers plots of (a) Aβ42 concentrations, (b) Aβ42/Aβ40 ratios, (c) pTau181 concentrations, and (d) pT181/Aβ42 ratios. All values are expressed in pg/mL, with the exception of the Aβ42/Aβ40 and pTau181/Aβ42 ratios. Each point corresponds to an individual value. Significant differences were assessed using the Kruskal–Wallis test followed by Steel–Dwass–Critchlow–Fligner test: n = 28 AD; n = 9 FTD; n = 4 MCI; n = 3 VAD; n = 5 Parkinsonism. Abbreviations: Aβ, Amyloid beta; pTau181, tau protein phosphorylated at residue 181.

Figure 5

Diagnostic performance of plasma biomarker. ROC curves describing the ability of plasma biomarkers to discriminate between (a) A+ from A− and (b) A+T+ from A−T− subjects. Each ROC curve is quantified by its AUC, shown in parentheses for the corresponding biomarker. Abbreviations: Aβ, Amyloid beta; pTau181, tau protein phosphorylated at residue 181; ROC, receiver operating characteristic, AUC, area under the curve.