Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer's Disease and Frontotemporal Dementia

Abstract

Alzheimer's disease (AD) is the primary type of dementia, followed by frontotemporal lobar degeneration (FTLD). They share some clinical characteristics, mainly at the early stages. So, the identification of early, specific, and minimally invasive biomarkers is required. In this study, some plasma biomarkers (Amyloid β42, p-Tau181, t-Tau, neurofilament light (NfL), TAR DNA-binding protein 43 (TDP-43)) were determined by single molecule array technology (SIMOA^®) in control subjects (n = 22), mild cognitive impairment due to AD (MCI-AD, n = 33), mild dementia due to AD (n = 12), and FTLD (n = 11) patients. The correlations between plasma and cerebrospinal fluid (CSF) levels and the accuracy of plasma biomarkers for AD early diagnosis and discriminating from FTLD were analyzed. As result, plasma p-Tau181 and NfL levels correlated with the corresponding CSF levels. Additionally, plasma p-Tau181 showed good accuracy for distinguishing between the controls and AD, as well as discriminating between AD and FTLD. Moreover, plasma NfL could discriminate dementia-AD vs. controls, FTLD vs. controls, and MCI-AD vs. dementia-AD. Therefore, the determination of these biomarkers in plasma is potentially helpful in AD spectrum diagnosis, but also discriminating from FTLD. In addition, the accessibility of these potential early and specific biomarkers may be useful for AD screening protocols in the future.

Keywords: Alzheimer’s disease; SIMOA; biomarker; diagnosis; frontotemporal dementia; plasma.

Figure 1

Box plots representing the plasma levels in the different participants groups (healthy controls (HC), MCI-AD, dementia-AD, FTLD). (a) Aβ40; (b) Aβ42; (c) p-Tau181; (d) t-Tau; (e) NfL; (f) TDP-43 (g) ratio Aβ42/Aβ40; (h) ratio t-Tau/Aβ42.

Figure 2

Receiver operating characteristic (ROC) curves for the PLS models developed from plasma biomarkers levels. (1) HC vs. MCI-AD; (2) HC vs. AD (MCI-AD + dementia-AD); (3) MCI-AD vs. FTLD; (4) AD (dementia-AD + MCI-AD) vs. FTLD.