Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness. Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD. This study aims to investigate the specific relationship between the AD biomarkers currently used in clinical practice and the plasma biomarkers. METHODS: In a memory clinic cohort, we analysed plasma pTau181, pTau217, pTau231, respectively, GFAP, NfL, CSF pTau181, Aβ-PET scans, and MRI/CT visual read of atrophy. We utilized methods based on multiple linear regression to evaluate the specific associations between clinically used and recently developed plasma biomarkers, while also considering demographic variables such as age and sex. FINDINGS: Although plasma pTau181, pTau217, pTau231, and GFAP were significantly associated with both Aβ-PET and CSF pTau181, Aβ-PET explained more variance in the levels of these biomarkers. The effect of CSF pTau181 on plasma GFAP and pTau181 was completely attenuated by Aβ-PET, whereas pTau231 and pTau217 were affected by both Aβ-PET and CSF pTau181 levels. Unlike these biomarkers, increased NfL was rather indicative of brain atrophy and older age. Based on the effect sizes, plasma pTau217 emerged as highly effective in distinguishing between A+ and A-, and T+ and T- individuals, with 60% of variance in plasma pTau217 explained by clinical AD biomarkers. INTERPRETATION: Amyloid burden primarily drives the changes in plasma pTau181, pTau217, pTau231, and GFAP. In contrast to plasma pTau217, a significant portion of variance in plasma pTau181, pTau231, GFAP, NfL remains unexplained by clinical AD biomarkers. FUNDING: This research is supported by the Swedish Research Council VR: 2017-06086, 2020-4-3018, 2024-2027; Swedish Brain Foundation, Swedish Alzhzeimer Foundation, CIMED Region Stockholm/Karolinska Institutet; the Region Stockholm - Karolinska Institutet regional agreement on medical training and clinical research (ALF), Fondation Recherche sur Alzheimer (France).
Source: EBioMedicine
Institutions: Karolinska Institutet, Karolinska University Hospital, Turku University Hospital, Turku PET Centre, University of Gothenburg, King's College London, South London and Maudsley NHS Foundation Trust, Stavanger University Hospital, University of Wisconsin–Madison, Sahlgrenska University Hospital, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,000
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Gun och Bertil Stohnes Stiftelse, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, Rainwater Charitable Foundation, National Institute for Health and Care Research, University College London, European Commission, Stiftelsen för Strategisk Forskning, Hjärnfonden, Karolinska Institutet, Vetenskapsrådet, NordForsk, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Kirsten og Freddy Johansens Fond, Alzheimerfonden, UK Dementia Research Institute, Olav Thon Stiftelsen, Fondation pour la Recherche sur Alzheimer, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme, Horizon 2020, Center for Innovative Medicine, National Institute on Aging, H2020 Marie Skłodowska-Curie Actions
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OpenAlex ID: W4405535264