The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease
Joel Simrén, Antoine Leuzy, Thomas K. Karikari, Abdul Hye, Andréa Lessa Benedet, Juan Lantero‐Rodriguez, Niklas Mattsson, Michael Schöll, Patrizia Mecocci, Bruno Vellas, Magda Tsolaki, Iwona Kłoszewska, Hilkka Soininen, Simon Lovestone, Dag Aarsland, Oskar Hansson, Pedro Rosa‐Neto, Eric Westman, Kaj Blennow, Henrik Zetterberg, Nicholas J. Ashton
Abstract
INTRODUCTION: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. METHODS: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. RESULTS: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. DISCUSSION: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.