A2 Refereed review article in a scientific journal
Clinical translation of fluid, imaging, and digital biomarkers for Alzheimer’s disease
Authors: Bacci, Julia R.; Karagianni, Stamatia; Alexopoulou, Zampeta-Sofia; Moukaled, Shirine; Tato-Fernández, Claudia; Arunachalam, Prithvi; Aslanyan, Aram; Aye, Sandar; Rocha, Ana Sabsil Lopez; Crugel, Monica; Fawad, Ayesha; Sogorb-Esteve, Aitana; Schöll, Michael; König, Alexandra; Paterson, Ross W.
Conference name: Brain & Brain PET
Publication year: 2026
Journal: Alzheimer's Research and Therapy
Article number: 14
Volume: 18
ISSN: 0271-678X
eISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-025-01921-5
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/10.1186/s13195-025-01921-5
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/508176997
Self-archived copy's licence: CC BY NC ND
Self-archived copy's version: Publisher`s PDF
Background: The Centiloid (CL) scale was developed to harmonise the quantification of amyloid-beta (Ab) positron emission tomography (PET) and is currently widely implemented in Alzheimer’s research. However, this scale could remain vulnerable to effects beyond image analysis.
Aim: The purpose of the present study was to determine the reliability of the transformation of [11C]PiB PET data acquired at Turku PET Centre to the CL scale.
Method: First-level calibration anchor points were calculated following the CL standard method with 45 Alzheimer’s disease patients and 34 young controls from the Global Alzheimer’s Association Interactive Network (GAAIN) dataset. The GAAIN dataset was re-processed with Turku PET Centre’s pipeline Magia (Karjalainen et al., 2020) for level-2 calibration of a non-standard image analysis method. Standardized uptake value ratios (SUVRs) were referenced to the whole cerebellum (WC) and the corrected cerebellar grey matter (cCG). The direct equations for CL conversion were applied to 101 [11C]PiB PET scans from cognitively healthy older adults (mean age 71.3 years, 59.4% females, 60.4% APOE4 carriers) acquired with a High-Resolution Research Tomograph. A data-driven threshold for Ab positivity was extracted from each method with a gaussian mixture model.
Result: First and second level analyses with the calibration dataset yielded a slope and correlation coefficient near unity (y=0.999x+0.075, R2=0.997, and y=1.01x+0.096, R2=0.961, respectively). Values referenced to WC resulted in a threshold of 25.43 CL, in accordance with the proposed CL threshold of 24–30 CL. However, direct conversion of SUVRs referenced to cCG resulted in higher CLs, compared to WC reference region, with a data-driven threshold of 41.18 CL for Ab positivity.
Conclusions: Transformation of [11C]PiB PET data processed with non-standard pipelines to CLs is possible, but affected by the choice of reference region. SUVRs referenced to WC appear to be more generalisable.
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Funding information in the publication:
Funding for the Biomarkers in Neurodegenerative Diseases course was provided by Gates Ventures. RWP is supported by the UCLH Queen Square Biomedical Research Centre, The UK Dementia Research Institute, an Alzheimer’s Association Part the Cloud award (PTC-22-982162) and a Rosetrees Race Against Dementia Teams award supported by the Q Charitable Trust. MS receives funding from the Knut and Alice Wallenberg Foundation (Wallenberg Centre for Molecular and Translational Medicine; KAW2014.0363 and KAW2023.0371), the Swedish Research Council (2017–02869, 2021–02678, 2021–06545 and 2023–06188), the European Union’s Horizon Europe research and innovation program under grant agreement no 101132933 (AD-RIDDLE) and 101112145 (PROMINENT), the National Institute of Health (R01 AG081394-01), Gates Ventures, the National Research Foundation of Korea (RS-2023-00263612), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG-813971 and ALFGBG-965326), the Swedish Brain Foundation (FO2021-0311 and FO2024-0372), the Swedish Alzheimer Foundation (AF-1011738), Familjen Rönström’s Foundation, the Sahlgrenska Academy at the University of Gothenburg, the Västra Götaland Region R&D (VGFOUREG-995510) and Innovation platforms, Sahlgrenska Science Park and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre.
MS has served/serves on advisory boards for Arvakor, Eli Lilly and Company, Novo Nordisk and Roche, received honoraria for presentations or educational material from Bioarctic, Novo Nordisk, Eli Lilly and Company, Roche and Triolabs, and receives research support (to the institution) from Beckman Coulter, Bioarctic, Novo Nordisk and Roche. He is co-founder and shareholder of Centile Bioscience and serves as Associate Editor with Alzheimer’s Research & Therapy.
