Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer’s and coronary disease pathways

Wang, Lihua; Western, Daniel; Timsina, Jigyasha; Repaci, Charlie; Song, Won‐Min; Norton, Joanne; Kohlfeld, Pat; Budde, John; Climer, Sharlee; Butt, Omar H.; Jacobson, Daniel; Garvin, Michael R.; Templeton, Alan R.; Campagna, Shawn R.; O’Halloran, Jane A.; Presti, Rachel; Goss, Charles W.; Mudd, Philip A.; Ances, Beau M.; Zhang, Bin; Sung, Yun Ju; Cruchaga, Carlos

doi:10.1016/j.isci.2023.106408

Cited by 11 publications

(21 citation statements)

References 93 publications

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“…We found SARS-CoV-2 infection to be associated with greater reductions in Aβ42:Aβ40 between pre-pandemic and pandemic assessment visits. These directions of change, which are associated with increased AD risk, were reported previously for acute COVID-19 cases (15,40). Moreover, correlated decreases in plasma Aβ42 and increases in pTau-181 were seen in older participants and those with MRI brain signatures of AD, adding to evidence of greater AD-related pathology and risks of future AD (13,28,29,41).…”

Section: Discussionsupporting

confidence: 86%

“…CoV-2 infection application of the more general Olink plasma protein-based risk scores developed in an earlier UK Biobank study also provide evidence for greater predicted risks for diabetes, ischaemic stroke and heart disease, COPD, lung cancer and endometriosis in the subset of participants under the age of 72 (16). This is consistent with emerging post-COVID-19 epidemiology data (49)(50)(51)(52) and proteomic studies of samples from COVID-19 patients hospitalised with acute symptoms (15). These fluid biomarkers have not been reported previously in a prospective SARS-CoV-2 infection or COVID-19 case-control setting.…”

Section: In Addition To Highlighting Increased Biomarker Indicators O...supporting

confidence: 90%

“…However, the global scale of the pandemic makes better understanding of the potential impact of COVID-19 for future dementias and other disease a public health priority (10,12). Recently developed high-throughput plasma proteomic biomarkers provide biologicallybased markers of risk predictive of risk or the onset of disease years in advance of a clinical diagnosis or even major symptomology (13)(14)(15)(16)(17)(18)(19). Amongst the best characterised plasma proteomic markers that are more specific for dementias are a relatively low beta amyloid-(1-42) (Aβ 42 ) and its ratio with beta amyloid-1-40) (Aβ 42 :Aβ 40 ), high phosphorylated tau (pTau) proteins, high neurofilament light (NFL) (a non-specific marker of neuronal injury) and glial fibrillary acidic protein (GFAP), which is associated with astrocyte activation.…”

Section: Introductionmentioning

confidence: 99%

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Plasma proteomic evidence for increased Alzheimer’s disease-related brain pathology after SARS-CoV-2 infection

Duff,

Zetterberg,

Heslegrave

et al. 2024

Preprint

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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 Aβ42:Aβ40 concentration ratio. In older participants, SARS-CoV-2 infection was associated with both lower plasma Aβ42 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.

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Section: Discussionsupporting

confidence: 86%

Section: In Addition To Highlighting Increased Biomarker Indicators O...supporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma proteomic evidence for increased Alzheimer’s disease-related brain pathology after SARS-CoV-2 infection

Duff,

Zetterberg,

Heslegrave

et al. 2024

Preprint

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“…The GOLM2 gene, also referred to as CASC4 and identi ed as a potential cancer susceptibility gene 39 , has been linked to reduced overall survival rates in ovarian cancer 40 . Recent studies conducted during the pandemic have highlighted the GOLM gene family, including GOLM1 and GOLM2, identifying them as potential causal plasma proteins associated with SARS-CoV-2 and suggesting their involvement in increased susceptibility to COVID-19 infection 41,42 .…”

Section: Discussionmentioning

confidence: 99%

Unveiling Genetic Signatures Associated with Resilience to Neonatal Diarrhea in Lambs Through Dual GWAS Approaches

Yaman,

Kişi,

Şengül

et al. 2024

Preprint

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Neonatal diarrhea poses a particularly daunting challenge due to its multifactorial etiology, resulting in high morbidity and mortality rates and substantial economic consequences worldwide. Moreover, the zoonotic potential of neonatal diarrhea underscores its importance in public health concerns. Although no molecular-level study has evaluated genetic resistance/susceptibility to neonatal diarrhea in farm animals, previous observations suggest potential avenues for further research. The present study employs two genome-wide association approaches, namely the nonparametric multi-locus (pKWmEB) and the single-locus Mixed Linear Model (MLM), to explore potential associations between genetic variations in innate immunity and neonatal diarrhea in Karacabey Merino lambs. A total of 707 lambs, comprising 180 cases and 527 controls, were analyzed, revealing an overall prevalence rate of 25.5%. Using a multi-locus (pKWmEB) GWA analysis, 13 SNPs surpassing the threshold of ≥ LOD 3 were identified. Additionally, the single-locus MLM approach identified one SNP with an exact p-value of 1.85e-7, and this SNP (s61781.1) in the SLC22A8 gene was co-detected by both methods. Our results demonstrate that besides environmental conditions and management practices, the manifestation of neonatal diarrhea can be explained to some degree by genetic backgrounds, and marker-assisted selection can be a useful complementary tool in the struggle against neonatal diarrhea.

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“…Predictive models built using machine learning approaches in neurodegenerative diseases tend to contain a large number of features, 40 , 45 or contain only the identified DE genes, transcripts, or proteins. 63 , 64 In here, we focused on models with a relatively low number of transcripts without compromising accuracy to maximize their potential to be translated to the clinic. Previous models using cfRNA reported an AUC of 0.83 for clinical AD; by substantially reducing the number of transcripts, we have increased the AUC up to 0.94 for presymptomatic AD and using only 220 transcripts.…”

Section: Discussionmentioning

confidence: 99%

Cell-free RNA signatures predict Alzheimer’s disease

Cisterna-García,

Beric,

Ali

et al. 2023

iScience

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Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer’s and coronary disease pathways

Cited by 11 publications

References 93 publications

Plasma proteomic evidence for increased Alzheimer’s disease-related brain pathology after SARS-CoV-2 infection

Plasma proteomic evidence for increased Alzheimer’s disease-related brain pathology after SARS-CoV-2 infection

Unveiling Genetic Signatures Associated with Resilience to Neonatal Diarrhea in Lambs Through Dual GWAS Approaches

Cell-free RNA signatures predict Alzheimer’s disease

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