Plasma p-tau181 as a promising non-invasive biomarker of Alzheimer's Disease pathology in Subjective Cognitive Decline and Mild Cognitive Impairment

Giulia Giacomucci; Salvatore Mazzeo; Chiara Crucitti; Assunta Ingannato; Silvia Bagnoli; Sonia Padiglioni; Giulia Galdo; Filippo Emiliani; Daniele Frigerio; Valentina Moschini; Carmen Morinelli; Sandro Sorbi; Valentina Bessi; Benedetta Nacmias

doi:10.1016/j.jns.2023.120805

Plasma p-tau181 as a promising non-invasive biomarker of Alzheimer's Disease pathology in Subjective Cognitive Decline and Mild Cognitive Impairment

J Neurol Sci. 2023 Oct 15:453:120805. doi: 10.1016/j.jns.2023.120805. Epub 2023 Sep 12.

Affiliations

¹ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
² Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
³ Regional Referral Centre for Relational Criticalities - Tuscany Region, Italy; Research and Innovation Centre for Dementia-CRIDEM, AOU Careggi, Italy.
⁴ SOD Neurologia I, Dipartimento Neuromuscolo-Scheletrico e degli Organi di Senso, AOU Careggi, Florence, Italy.
⁵ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. Electronic address: valentina.bessi@unifi.it.

PMID: 37716237
DOI: 10.1016/j.jns.2023.120805

Abstract

Introduction: The aim of this study is to investigate the role of plasma phosphorylated tau (p-tau) 181 as a potential biomarker for Alzheimer's Disease (AD) pathology in the early stages of the disease, as a valuable marker for tauopathy.

Materials and methods: Thirty-three Subjective Cognitive Decline (SCD), 32 Mild Cognitive Impairment (MCI) and 14 AD demented (AD-d) patients underwent plasma p-tau181 analysis with SiMoA assay. Twenty-six SCD, 32 MCI and 14 AD-d patients also underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) when A+ was associated with T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system.

Results: Plasma p-tau181 levels were higher in SCD AP+ than in SCD AP- (2.85 ± 0.53 vs 1.73 ± 0.64, p < 0.001), and in MCI AP+ than in MCI AP- (4.03 ± 1.07 vs 2.04 ± 0.87, p < 0.001). In a multivariate linear regression analysis, AP status was the only variable that influenced plasma p-tau181 (B = 1.670 [95% CI 1.097:2.244], p < 0.001). Plasma p-tau181 was highly accurate for discriminating between AP+ and AP- patients (AUC = 0.910). We identified a cut-off level of 2.69 pg/mL to distinguish between AP+ and AP- (sensibility 0.86, specificity 0.82, PPV 75.00% NPV 90.32%).

Conclusions: Plasma p-tau181 levels were influenced by the presence of underlying AD pathology, independently from the cognitive status and were highly accurate in differentiating SCD-MCI patients who were carriers of AD pathology from non-carriers. Plasma p-tau181 might be a promising non-invasive biomarker of AD pathology at a very early stage.

Keywords: Alzheimer's disease; Mild cognitive impairment; Plasma biomarkers; Plasma p-tau181; Subjective cognitive decline.