Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals

Pamela C L Ferreira; Joseph Therriault; Cécile Tissot; João Pedro Ferrari-Souza; Andréa L Benedet; Guilherme Povala; Bruna Bellaver; Douglas T Leffa; Wagner S Brum; Firoza Z Lussier; Gleb Bezgin; Stijn Servaes; Marie Vermeiren; Arthur C Macedo; Arlec Cabrera; Jenna Stevenson; Gallen Triana-Baltzer; Hartmuth Kolb; Nesrine Rahmouni; William E Klunk; Oscar L Lopez; Victor L Villemagne; Ann Cohen; Dana L Tudorascu; Eduardo R Zimmer; Thomas K Karikari; Nicholas J Ashton; Henrik Zetterberg; Kaj Blennow; Serge Gauthier; Pedro Rosa-Neto; Tharick A Pascoal

doi:10.1002/alz.13393

Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals

Alzheimers Dement. 2023 Oct;19(10):4463-4474. doi: 10.1002/alz.13393. Epub 2023 Aug 3.

Authors

Pamela C L Ferreira¹, Joseph Therriault^{2

3}, Cécile Tissot^{1

2

3}, João Pedro Ferrari-Souza^{1

4}, Andréa L Benedet^{5

6}, Guilherme Povala¹, Bruna Bellaver^{1

4}, Douglas T Leffa¹, Wagner S Brum^{4

5

6}, Firoza Z Lussier¹, Gleb Bezgin^{2

3}, Stijn Servaes^{2

3}, Marie Vermeiren^{2

3}, Arthur C Macedo^{2

3}, Arlec Cabrera¹, Jenna Stevenson^{2

3}, Gallen Triana-Baltzer⁷, Hartmuth Kolb⁷, Nesrine Rahmouni^{2

3}, William E Klunk¹, Oscar L Lopez¹, Victor L Villemagne¹, Ann Cohen¹, Dana L Tudorascu^{1

8

9}, Eduardo R Zimmer^{4

10

11

12}, Thomas K Karikari^{1

5

6}, Nicholas J Ashton^{5

6

13

14}, Henrik Zetterberg^{5

6

15

16

17

18}, Kaj Blennow^{5

6}, Serge Gauthier³, Pedro Rosa-Neto^{2

3}, Tharick A Pascoal^{1

19}

Affiliations

¹ Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
² Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Hospital Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montréal, Québec, Canada.
³ Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
⁴ Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
⁵ Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Neuroscience Biomarkers, Janssen Research and Development, La Jolla, California, USA.
⁸ Department of Intelligent Systems, University of Pittsburgh, Pittsburgh, USA.
⁹ Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Graduate Program in Biological Sciences: Pharmacology and Therapeuctis, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
¹¹ Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
¹² Brain Institute of Rio Grande do Sul, PUCRS, Porto Alegre, Rio Grande do Sul, Brazil.
¹³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
¹⁴ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁵ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
¹⁶ UK Dementia Research Institute at UCL, London, UK.
¹⁷ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, Hong Kong, China.
¹⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹⁹ Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abstract

Introduction: Phosphorylated tau (p-tau) biomarkers have been recently proposed to represent brain amyloid-β (Aβ) pathology. Here, we evaluated the plasma biomarkers' contribution beyond the information provided by demographics (age and sex) to identify Aβ and tau pathologies in individuals segregated as cognitively unimpaired (CU) and impaired (CI).

Methods: We assessed 138 CU and 87 CI with available plasma p-tau231, 217⁺ , and 181, Aβ42/40, GFAP and Aβ- and tau-PET.

Results: In CU, only plasma p-tau231 and p-tau217⁺ significantly improved the performance of the demographics in detecting Aβ-PET positivity, while no plasma biomarker provided additional information to identify tau-PET positivity. In CI, p-tau217⁺ and GFAP significantly contributed to demographics to identify both Aβ-PET and tau-PET positivity, while p-tau231 only provided additional information to identify tau-PET positivity.

Discussion: Our results support plasma p-tau231 and p-tau217⁺ as state markers of early Aβ deposition, but in later disease stages they inform on tau tangle accumulation.

Highlights: It is still unclear how much plasma biomarkers contribute to identification of AD pathology across the AD spectrum beyond the information already provided by demographics (age + sex). Plasma p-tau231 and p-tau217⁺ contribute to demographic information to identify brain Aβ pathology in preclinical AD. In CI individuals, plasma p-tau231 contributes to age and sex to inform on the accumulation of tau tangles, while p-tau217⁺ and GFAP inform on both Aβ deposition and tau pathology.

Keywords: PET; demographics; p-tau; plasma biomarkers; tau pathology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease*
Amyloid beta-Peptides*
Biomarkers
Humans
Plasma
Positron-Emission Tomography
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding