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

Eugene P Duff ^1,2, Henrik Zetterberg ^3,4,5,6,7,8, Amanda Heslegrave ⁵

¹UK Dementia Research Institute Centre at Imperial College London, London, UK. e.duff@imperial.ac.uk.
²Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. e.duff@imperial.ac.uk.
³Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
⁴Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
⁶UK Dementia Research Institute Centre at UCL, London, UK.
⁷Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
⁸Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁹UK Dementia Research Institute Centre at Imperial College London, London, UK.
¹⁰Department of Epidemiology and Biostatistics, Faculty of Medicine, Imperial College London, London, UK.
¹¹MRC Centre for Environment and Health, Imperial College London, London, UK.
¹²British Heart Foundation Centre of Research Excellence, Imperial College London, London, UK.
¹³National Institute for Health Research Biomedical Research Centre, Imperial College London, London, UK.
¹⁴Health Data Research UK at Imperial College London, London, UK.
¹⁵Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹⁶UK Biobank, Stockport, UK.
¹⁷Translational Sciences, Biogen, Cambridge, MA, USA.
¹⁸Neuroscience Data Science, Janssen Research & Development, Cambridge, MA, USA.
¹⁹UK Dementia Research Institute Centre at Imperial College London, London, UK. p.matthews@imperial.ac.uk.
²⁰Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. p.matthews@imperial.ac.uk.
²¹The Rosalind Franklin Institute, Didcot, UK. p.matthews@imperial.ac.uk.

⁰UK Dementia Research Institute Centre at Imperial College London, London, UK. e.duff@imperial.ac.uk.

Nature Medicine +

|

January 30, 2025

View abstract on PubMed

Summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may increase Alzheimer's disease risk. This study found SARS-CoV-2 associated with biomarkers of brain amyloid pathology in older adults.

Area Of Science

Neuroscience
Infectious Diseases
Gerontology

Background

Systemic viral infections are linked to increased dementia risk.
The association between SARS-CoV-2 and dementia risk remains unclear.
Understanding this link is crucial for predicting future dementia incidence.

Purpose Of The Study

To investigate the association between SARS-CoV-2 infection and Alzheimer's disease (AD) biomarkers.
To determine if SARS-CoV-2 infection impacts biomarkers related to amyloid pathology.
To explore the relationship between SARS-CoV-2, AD biomarkers, and cognitive/neurological outcomes.

Main Methods

Utilized UK Biobank data, measuring plasma biomarkers before and after serology-confirmed SARS-CoV-2 infection.
Analyzed biomarkers associated with Alzheimer's disease pathology, including Aβ42:Aβ40 ratio, Aβ42, and pTau-181.
Correlated biomarker changes with brain imaging, cognitive test scores, and overall health evaluations.

Main Results

SARS-CoV-2 infection was linked to reduced plasma Aβ42:Aβ40 ratio, indicating increased amyloid pathology.
Lower plasma Aβ42 and higher plasma pTau-181 were observed in more vulnerable participants.
Biomarker changes correlated with brain structural patterns of AD, reduced cognitive function, and poorer health.

Conclusions

Observational biomarker evidence suggests SARS-CoV-2 infection is associated with increased brain β-amyloid pathology in older adults.
The association was more pronounced in individuals hospitalized with COVID-19 or with prior hypertension.
Findings suggest SARS-CoV-2 may elevate the risk of future Alzheimer's disease, warranting further investigation into systemic inflammatory diseases.

Related Concept Videos

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...