Novel blood test for early biomarkers of preeclampsia and Alzheimer's disease.
Adult
Alzheimer Disease
/ blood
Amyloid beta-Peptides
Biomarkers
/ blood
Blood Chemical Analysis
/ methods
Blood Proteins
/ analysis
Cognitive Dysfunction
/ diagnosis
Female
Hematologic Tests
/ methods
Humans
Immunohistochemistry
Peptide Fragments
Pre-Eclampsia
/ blood
Pregnancy
Protein Aggregates
/ physiology
ROC Curve
Trophoblasts
/ drug effects
alpha-Synuclein
tau Proteins
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 08 2021
05 08 2021
Historique:
received:
18
03
2021
accepted:
19
07
2021
entrez:
6
8
2021
pubmed:
7
8
2021
medline:
16
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34354200
doi: 10.1038/s41598-021-95611-5
pii: 10.1038/s41598-021-95611-5
pmc: PMC8342418
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Blood Proteins
0
Peptide Fragments
0
Protein Aggregates
0
alpha-Synuclein
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15934Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM121298
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058648
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM114750
Pays : United States
Informations de copyright
© 2021. The Author(s).
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