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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2021
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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) |
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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 |
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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 |
work_keys_str_mv |
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