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Nature medicine
Published

Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection

Authors

Eugene P Duff, Henrik Zetterberg, Amanda Heslegrave, Abbas Dehghan, Paul Elliott, Naomi Allen, Heiko Runz, Rhiannon Laban, Elena Veleva, Christopher D Whelan, Benjamin B Sun, Paul M Matthews

Abstract

Nat Med. 2025 Jan 30. doi: 10.1038/s41591-024-03426-4. Online ahead of print.

ABSTRACT

Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections is unknown. Determining this is important for anticipating the potential future incidence of dementia. To begin to do this, we measured plasma biomarkers linked to Alzheimer's disease pathology in the UK Biobank before and after serology-confirmed SARS-CoV-2 infections. SARS-CoV-2 infection was associated with biomarkers associated with β-amyloid pathology: reduced plasma Aβ42:Aβ40 ratio and, in more vulnerable participants, lower plasma Aβ42 and higher plasma pTau-181. The plasma biomarker changes were greater in participants who had been hospitalized with COVID-19 or had reported hypertension previously. We showed that the changes in biomarkers were linked to brain structural imaging patterns associated with Alzheimer's disease, lower cognitive test scores and poorer overall health evaluations. Our data from this post hoc case-control matched study thus provide observational biomarker evidence that SARS-CoV-2 infection can be associated with greater brain β-amyloid pathology in older adults. While these results do not establish causality, they suggest that SARS-CoV-2 (and possibly other systemic inflammatory diseases) may increase the risk of future Alzheimer's disease.

PMID:39885359 | DOI:10.1038/s41591-024-03426-4

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg
Amanda Heslegrave

Dr Amanda Heslegrave

Principal Research Fellow

Co-leading the UK DRI Biomarker Factory platform based at UK DRI at UCL

Dr Amanda Heslegrave
Paul Elliott

Prof Paul Elliott

Group Leader

Using advanced methods in genetic, epidemiology and metabolic phenotyping to improve understanding of dementias

Prof Paul Elliott

Rhiannon Laban

Research Technician, UK DRI Biomarker Factory

Research Technician, UK DRI Biomarker Factory

Rhiannon Laban

Elena Veleva

UK DRI Facility Co-ordinator

Facility Co-ordinator, UK DRI Biomarker Factory

Elena Veleva