A1 Refereed original research article in a scientific journal
Early functional changes and plasma GFAP in Swedish families with Autosomal Dominant Alzheimer’s disease mutations
Authors: Luckett, Emma S.; Zapater-Fajari, Mariola; Almkvist, Ove; Johansson, Charlotte; Chiotis, Konstantinos; Bucci, Marco; Wall, Anders; Ashton, Nicholas J.; Blennow, Kaj; Zetterberg, Henrik; Rodriguez-Vieitez, Elena; Graff, Caroline; Nordberg, Agneta
Publisher: Springer Science and Business Media LLC
Publication year: 2026
Journal: Translational Psychiatry
Article number: 67
Volume: 16
eISSN: 2158-3188
DOI: https://doi.org/10.1038/s41398-026-03829-6
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://doi.org/10.1038/s41398-026-03829-6
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/508963278
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
We aimed to understand longitudinal associations between Alzheimer’s disease (AD) biomarkers in Autosomal Dominant AD (ADAD) across estimated years to symptom onset (EYO). Forty-five individuals (19 mutation carriers [EYO = −7.9 ± 11.7 years, APP N = 11; PSEN1 N = 8]) from Swedish ADAD families participated. All received baseline 18F-Flurodeoxyglucose (FDG) PET and cognitive testing, and a subset (N = 26) plasma glial fibrillary acidic protein (GFAP) measurement. Follow-up data collection (including 106 FDG scans) was performed over 7.4 ± 6.4 years (visits ranged from 1–5, EYO = −25.8 to +10.3 years in mutation carriers). Mixed effects models were applied to determine longitudinal associations. APP and PSEN1 mutation carriers showed different FDG uptake profiles from EYO = −20 to −10 years, with a hypermetabolism before hypometabolism in PSEN1 mutation carriers. Early increases in plasma GFAP were primarily related to subcortical FDG decreases and cognitive changes in APP mutation carriers compared to non-carriers. We provide evidence for gene-dependent biomarker trajectories in ADAD.
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Funding information in the publication:
AN was supported by grants from the Swedish Research Council (2017-02965,2017-06087, 2020-01990, 2023-02649), the Swedish Foundation for Strategic Research (SSF; RB13-0192), the Swedish Brain Foundation (Hjärnfonden), the Center for Innovative Medicine (CIMED) at Region Stockholm - Karolinska institutet, the Swedish Alzheimer Foundation (Alzheimerfonden), Fondation pour la Recherche sur Alzheimer, Paris, France, the Region Stockholm-Karolinska Institutet regional agreement on medical training and clinical research (ALF), private bequests. Rainwater foundation, US. CJ and CG were supported by grants from the Swedish Research Council (#529-2014-7504, #2015-02926, #2018-02754), the Swedish Brain Foundation, the Swedish Dementia Foundation (Demensfonden), the Swedish Alzheimer Foundation (Alzheimerfonden), ALF-Projects Region Stockholm, the Gun and Bertil Stohne’s Foundation and Stiftelsen för Gamla Tjänarinnor, Sweden. KB is supported by the Swedish Research Council (#2017-00915 and #2022-00732), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721, #AF-968270, and #AF-994551), Hjärnfonden, Sweden (#FO2017-0243 and #ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), the Alzheimer’s Association 2022-2025 Grant (SG-23-1038904 QC), La Fondation Recherche Alzheimer (FRA), Paris, France, the Kirsten and Freddy Johansen Foundation, Copenhagen, Denmark, and Familjen Rönströms Stiftelse, Stockholm, Sweden. HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the Bluefield Project, Cure Alzheimer’s Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Familjen Rönströms Stiftelse, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). Open access funding provided by Karolinska Institute.
