Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden

Juan Lantero-Rodriguez; Cécile Tissot; Anniina Snellman; Stijn Servaes; Andrea L Benedet; Nesrine Rahmouni; Laia Montoliu-Gaya; Joseph Therriault; Wagner S Brum; Jenna Stevenson; Firoza Z Lussier; Gleb Bezgin; Arthur C Macedo; Mira Chamoun; Sulantha S Mathotaarachi; Tharick A Pascoal; Nicholas J Ashton; Henrik Zetterberg; Pedro Rosa Neto; Kaj Blennow

doi:10.1002/alz.13119

Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden

Alzheimers Dement. 2023 Dec;19(12):5343-5354. doi: 10.1002/alz.13119. Epub 2023 May 15.

Authors

Juan Lantero-Rodriguez¹, Cécile Tissot^{2

3}, Anniina Snellman^{1

4}, Stijn Servaes^{2

3}, Andrea L Benedet¹, Nesrine Rahmouni^{2

3}, Laia Montoliu-Gaya¹, Joseph Therriault^{2

3}, Wagner S Brum^{1

5}, Jenna Stevenson^{2

3}, Firoza Z Lussier^{2

6}, Gleb Bezgin^{2

3}, Arthur C Macedo^{2

3}, Mira Chamoun^{2

3}, Sulantha S Mathotaarachi^{2

3}, Tharick A Pascoal⁶, Nicholas J Ashton^{1

7

8

9}, Henrik Zetterberg^{1

10

11

12

13

14}, Pedro Rosa Neto^{2

3}, Kaj Blennow^{1

10}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
² Translational Neuroimaging Laboratory, McGill Research Centre for Studies in Aging, Douglas Mental Health Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest de l'Île de Montréal, Montreal, Canada.
³ Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Canada.
⁴ Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland.
⁵ Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
⁶ Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁷ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁸ Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
⁹ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
¹² UK Dementia Research Institute, University College London, London, UK.
¹³ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹⁴ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 37190913
DOI: 10.1002/alz.13119

Abstract

Introduction: Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed.

Methods: We measured cerebrospinal fluid (CSF) and plasma concentrations of N-terminal tau fragments (NTA-tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (Aβ) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments.

Results: CSF and plasma NTA-tau concentrations were specifically increased in cognitively impaired Aβ-positive groups. CSF and plasma NTA-tau concentrations displayed stronger correlations with tau PET than with Aβ PET and MRI, both in global uptake and at the voxel level. Regression models demonstrated that both CSF and plasma NTA-tau are preferentially associated with tau pathology. Moreover, plasma NTA-tau was associated with longitudinal tau PET accumulation across the aging and Alzheimer's disease (AD) spectrum.

Discussion: NTA-tau is a biomarker closely associated with in vivo tau deposition in the AD continuum and has potential as a tau tangle biomarker in clinical settings and trials.

Highlights: An assay for detecting N-terminal tau fragments (NTA-tau) in plasma and CSF was evaluated. NTA-tau is more closely associated with tau PET than amyloid PET or neurodegeneration. NTA-tau can successfully track in vivo tau deposition across the AD continuum. Plasma NTA-tau increased over time only in cognitively impaired amyloid-β positive individuals.

Keywords: Alzheimer's disease; NTA; biomarkers; cerebrospinal fluid; plasma; tau.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / diagnosis
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction* / diagnosis
Humans
Neurofibrillary Tangles / pathology
Positron-Emission Tomography / methods
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
tau Proteins
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding