Future perspective and clinical applicability of the combined use of plasma phosphorylated tau 181 and neurofilament light chain in Subjective Cognitive Decline and Mild Cognitive Impairment

• Published in: Scientific reports Vol. 14; no. 1; pp. 11307 - 12
• Main Authors: Giacomucci, Giulia, Mazzeo, Salvatore, Ingannato, Assunta, Crucitti, Chiara, Bagnoli, Silvia, Padiglioni, Sonia, Romano, Lucrezia, Galdo, Giulia, Emiliani, Filippo, Frigerio, Daniele, Ferrari, Camilla, Moschini, Valentina, Morinelli, Carmen, Notarelli, Antonella, Sorbi, Sandro, Nacmias, Benedetta, Bessi, Valentina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-05-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/617; 692/617/375/132; Accuracy; Aged; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers; Biomarkers - blood; Cerebrospinal fluid; Cognitive ability; Cognitive Dysfunction - blood; Cognitive Dysfunction - diagnosis; Female; Humanities and Social Sciences; Humans; Male; Middle Aged; Mild Cognitive Impairment; multidisciplinary; Neurodegenerative diseases; Neurofilament Proteins - blood; NfL; p-tau181; Pathology; Phosphorylation; Plasma; Plasma biomarkers; Science; Science (multidisciplinary); Subjective Cognitive Decline; Tau protein; tau Proteins - blood; tau Proteins - cerebrospinal fluid; Alzheimer’s Disease; p-tau181; Mild Cognitive Impairment; Plasma biomarkers; NfL; Subjective Cognitive Decline
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-61655-6

We aimed to assess diagnostic accuracy of plasma p-tau181 and NfL separately and in combination in discriminating Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) patients carrying Alzheimer’s Disease (AD) pathology from non-carriers; to propose a flowchart for the interpretation of the results of plasma p-tau181 and NfL. We included 43 SCD, 41 MCI and 21 AD-demented (AD-d) patients, who underwent plasma p-tau181 and NfL analysis. Twenty-eight SCD, 41 MCI and 21 AD-d patients underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1–40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) it they were A+/T+ , or non-carriers (AP−) when they were A−, A+/T−/N−, or A+/T−/N+ according to the A/T(N) system. Plasma p-tau181 and NfL separately showed a good accuracy (AUC = 0.88), while the combined model (NfL + p-tau181) showed an excellent accuracy (AUC = 0.92) in discriminating AP+ from AP− patients. Plasma p-tau181 and NfL results were moderately concordant (Coehn’s k = 0.50,
p
 < 0.001). Based on a logistic regression model, we estimated the risk of AD pathology considering the two biomarkers: 10.91% if both p-tau181 and NfL were negative; 41.10 and 76.49% if only one biomarker was positive (respectively p-tau18 and NfL); 94.88% if both p-tau181 and NfL were positive. Considering the moderate concordance and the risk of presenting an underlying AD pathology according to the positivity of plasma p-tau181 and NfL, we proposed a flow chart to guide the combined use of plasma p-tau181 and NfL and the interpretation of biomarker results to detect AD pathology.