Plasma Phosphorylated Tau 231 Increases at One-Year Intervals in Cognitively Unimpaired Subjects

Article type: Research Article

Authors: Martínez-Dubarbie, Francisco^{a; b; *} | López-García, Sara^{a; b} | Lage, Carmen^{a; b; c} | Di Molfetta, Guglielmo^d | Fernández-Matarrubia, Marta^{a; b} | Pozueta-Cantudo, Ana^{a; b} | García-Martínez, María^{a; b} | Corrales-Pardo, Andrea^{a; b} | Bravo, María^{a; b} | Jiménez-Bonilla, Julio^e | Quirce, Remedios^e | Marco de Lucas, Enrique^f | Drake-Pérez, Marta^f | Tordesillas, Diana^f | López-Hoyos, Marcos^{b; g} | Irure-Ventura, Juan^{b; g} | Valeriano-Lorenzo, Elizabeth^h | Blennow, Kaj^{d; i} | Ashton, Nicholas J.^{d; j; k; l} | Zetterberg, Henrik^{d; i; m; n; o; p} | Rodríguez-Rodríguez, Eloy^{a; b; q} | Sánchez-Juan, Pascual^{h; q}

Affiliations: [a] Neurology Service, Marqués de Valdecilla University Hospital, Santander, Spain | [b] Institute for Research Marqués de Valdecilla (IDIVAL), Santander, Spain | [c] Atlantic Fellow for Equity in Brain health, Global Brain Health Institute, University of California, San Francisco, CA, USA | [d] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden | [e] Nuclear Medicine Department, Marqués de Valdecilla University Hospital, University of Cantabria and Institute for Research Marqués de Valdecilla (IDIVAL), Santander, Spain | [f] Radiology Department, Marqués de Valdecilla University Hospital, Santander, Spain | [g] Immunology Department, Marqués de Valdecilla University Hospital, Santander, Spain | [h] Alzheimer’s Centre Reina Sofia-CIEN Foundation-ISCIII, Madrid, Spain | [i] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden | [j] Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway | [k] King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK | [l] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK | [m] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK | [n] UK Dementia Research Institute at UCL, London, UK | [o] Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China | [p] Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [q] CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain

Correspondence: [*] Correspondence to: Francisco Martínez-Dubarbie, MD, Neurology Service, Marqués de Valdecilla University Hospital, Avda. de Valdecilla 25, 39008, Santander, Cantabria, Spain. Tel.: +34627158291; E-mail: [email protected]; ORCID: https://orcid.org/0000-0002-1482-7813.

Abstract: Background:Plasma biomarkers of Alzheimer’s disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective:With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters. Methods:We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers. Results:Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures. Conclusions:Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.

Keywords: Alzheimer’s disease, longitudinal study, p-tau231, plasma biomarkers, presymptomatic stages

DOI: 10.3233/JAD-231479

Journal: Journal of Alzheimer's Disease, vol. 98, no. 3, pp. 1029-1042, 2024