Amyloid and tau accumulate across distinct spatial networks and are differentially associated with brain connectivity

Abstract
Data availability
Article and author information
Metrics

Abstract

The abnormal accumulation of amyloid-β and tau targets specific spatial networks in Alzheimer's disease. However, the relationship between these networks across different disease stages and their association with brain connectivity has not been explored. In this study, we applied a joint independent component analysis to ¹⁸F- Flutemetamol (amyloid-β) and ¹⁸F-Flortaucipir (tau) PET images to identify amyloid-β and tau networks across different stages of Alzheimer's disease. We then assessed whether these patterns were associated with resting-state functional networks and white matter tracts. Our analyses revealed nine patterns that were linked across tau and amyloid-β data. The amyloid-b and tau patterns showed a fair to moderate overlap with distinct functional networks but only tau was associated with white matter integrity loss and multiple cognitive functions. These findings show that amyloid-b and tau have different spatial affinities, which can be used to understand how they accumulate in the brain and potentially damage the brain's connections.

Data availability

Source data files have been provided for Figures 4 and 5. The source data for the rest of the analyses performed in this study can be requested from Prof. Oskar Hansson (Oskar.Hansson@med.lu.se), after signing a material transfer agreement from Lund University that ensures that the data will only be used for the sole purpose of replicating procedures and results presented in the article and as long as data transfer is in agreement with EU legislation on the general data protection regulation and decisions by the Ethical Review Board of Sweden and Region Skåne.

Article and author information

Author details

Joana B Pereira

Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden

For correspondence
joana.pereira@ki.se

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4604-2711
Rik Ossenkoppele

Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands

Competing interests
No competing interests declared.
Sebastian Palmqvist

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden

Competing interests
No competing interests declared.
Tor Olof Strandberg

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden

Competing interests
No competing interests declared.
Ruben Smith

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden

Competing interests
No competing interests declared.
Eric Westman

Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden

Competing interests
No competing interests declared.
Oskar Hansson

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden

For correspondence
oskar.hansson@med.lu.se

Competing interests
Oskar Hansson, has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Biogen, Roche, and Fujirebio.

Funding

European Research Council, Swedish Research Council, Swedish Brain Foundation, Startneuro, Swedish Alzheimer Foundation, Knut and Alice Wallenberg foundation, Strategic Research Area Multipark

Oskar Hansson

Swedish Research Council, Alzheimerfonden, Swedish Brain Research

Joana B Pereira

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study received ethical approval from the Regional Ethical Review Board of Lund University (Dnr 2008-695, 2008-290, 2010-156), the Swedish Medicines and Products Agency (Dnr 151:2012/4552, 5.1-2014-62949), and the Radiation Safety Committee of Skåne University Hospital in Sweden. All participants provided informed consent before being included in the study.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.