Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease

Abstract A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer’s disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with...

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Autores principales: Shibin Cheng, Sayani Banerjee, Lori A. Daiello, Akitoshi Nakashima, Sukanta Jash, Zheping Huang, Jonathan D. Drake, Jan Ernerudh, Goran Berg, James Padbury, Shigeru Saito, Brian R. Ott, Surendra Sharma
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/a0e8b71cb20e4e69945cd735b39330f0
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spelling oai:doaj.org-article:a0e8b71cb20e4e69945cd735b39330f02021-12-02T17:06:09ZNovel blood test for early biomarkers of preeclampsia and Alzheimer’s disease10.1038/s41598-021-95611-52045-2322https://doaj.org/article/a0e8b71cb20e4e69945cd735b39330f02021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95611-5https://doaj.org/toc/2045-2322Abstract A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer’s disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE (n = 33 early onset and 33 late onset) and gestational age-matched controls (n = 77) as well as AD in both dementia and prodromal mild cognitive impairment (MCI, n = 24) stages with age-matched controls (n = 19). The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid β-42, α-synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity (PE; AUC: 1, CI: 0.949–1.00; AD; AUC: 0.986, CI: 0.832–1.00). In conclusion, we have developed a novel, noninvasive diagnostic and predictive assay for AD, MCI and PE.Shibin ChengSayani BanerjeeLori A. DaielloAkitoshi NakashimaSukanta JashZheping HuangJonathan D. DrakeJan ErnerudhGoran BergJames PadburyShigeru SaitoBrian R. OttSurendra SharmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shibin Cheng
Sayani Banerjee
Lori A. Daiello
Akitoshi Nakashima
Sukanta Jash
Zheping Huang
Jonathan D. Drake
Jan Ernerudh
Goran Berg
James Padbury
Shigeru Saito
Brian R. Ott
Surendra Sharma
Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
description Abstract A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer’s disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE (n = 33 early onset and 33 late onset) and gestational age-matched controls (n = 77) as well as AD in both dementia and prodromal mild cognitive impairment (MCI, n = 24) stages with age-matched controls (n = 19). The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid β-42, α-synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity (PE; AUC: 1, CI: 0.949–1.00; AD; AUC: 0.986, CI: 0.832–1.00). In conclusion, we have developed a novel, noninvasive diagnostic and predictive assay for AD, MCI and PE.
format article
author Shibin Cheng
Sayani Banerjee
Lori A. Daiello
Akitoshi Nakashima
Sukanta Jash
Zheping Huang
Jonathan D. Drake
Jan Ernerudh
Goran Berg
James Padbury
Shigeru Saito
Brian R. Ott
Surendra Sharma
author_facet Shibin Cheng
Sayani Banerjee
Lori A. Daiello
Akitoshi Nakashima
Sukanta Jash
Zheping Huang
Jonathan D. Drake
Jan Ernerudh
Goran Berg
James Padbury
Shigeru Saito
Brian R. Ott
Surendra Sharma
author_sort Shibin Cheng
title Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
title_short Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
title_full Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
title_fullStr Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
title_full_unstemmed Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
title_sort novel blood test for early biomarkers of preeclampsia and alzheimer’s disease
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/a0e8b71cb20e4e69945cd735b39330f0
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