Blood biomarkers of Alzheimer’s disease and progression across different stages of cognitive decline in the community

Martina Valletta (), Davide Liborio Vetrano, Caterina Gregorio, Debora Rizzuto, Bengt Winblad, Marco Canevelli, Sarah Andersson, Matilda Dale, Claudia Fredolini, Erika J. Laukka, Laura Fratiglioni and Giulia Grande
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Martina Valletta: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Davide Liborio Vetrano: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Caterina Gregorio: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Debora Rizzuto: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Bengt Winblad: Karolinska Institutet, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society
Marco Canevelli: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Sarah Andersson: Royal Institute of Technology (KTH), Affinity Proteomics Stockholm, Science for Life Laboratory, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH)
Matilda Dale: Royal Institute of Technology (KTH), Affinity Proteomics Stockholm, Science for Life Laboratory, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH)
Claudia Fredolini: Royal Institute of Technology (KTH), Affinity Proteomics Stockholm, Science for Life Laboratory, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH)
Erika J. Laukka: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Laura Fratiglioni: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society
Giulia Grande: Karolinska Institutet and Stockholm University, Aging Research Center, Department of Neurobiology, Care Sciences and Society

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract Blood biomarkers of Alzheimer’s disease (AD) are promising for dementia prediction, but their association with progression across intermediate stages of cognitive decline in the general population remains unclear. We followed 2148 dementia-free individuals from a Swedish population-based cohort for up to 16 years. Associations between baseline AD blood biomarkers and transitions between normal cognition, mild cognitive impairment (MCI), and dementia were examined. Lower amyloid-β42/40 ratio and higher phosphorylated-tau181 (p-tau181), p-tau217, total-tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were associated with faster progression from MCI to all-cause and AD dementia, with the strongest associations for NfL and p-tau217. Elevated NfL and GFAP were linked to reduced MCI reversion to normal cognition, whereas no biomarker was associated with MCI development from normal cognition. These findings show robust group-level associations and indicate that AD blood biomarkers may help stratify dementia risk at the MCI stage in the community.

Date: 2025
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DOI: 10.1038/s41467-025-66728-2

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