ABSTRACT
Viral infections have been linked to an increased risk for dementia. We investigated whether SARS-CoV-2 infection increases preclinical brain pathology associated with Alzheimer's disease (AD) by comparing changes in plasma biomarkers in UK Biobank participants with and without prior SARS-CoV-2 infection. We discovered an association between SARS-CoV-2 infection and reduced plasma A{beta}42:A{beta}40 concentration ratio. In older participants, SARS-CoV-2 infection was associated with both lower plasma A{beta}42 and higher plasma pTau-181. These biomarker changes, which have been associated with beta-amyloid accumulation and prodromal AD, were associated with increased brain imaging signatures of AD, poorer cognitive scores, and worse assessments of overall health and appeared to be greater in participants who had been hospitalised with COVID-19. Protein biomarker risk scores for other diseases were also raised among individuals who had past SARS-CoV-2 infections. Our data provide support for the hypothesis that viral infections can accelerate prodromal AD pathology and highlight biomarker profiles indicative of an increased risk of dementia and systemic diseases after SARS-CoV-2 infection, particularly in older people.