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

Abstract

AbstractNon-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. However, a blood test based on a mechanistic link to pathologic protein aggregate complexes has not been yet elucidated. 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 as well as AD in both dementia and prodromal mild cognitive impairment (MCI) stages. 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. Autophagy-proficient human trophoblasts failed to accumulate serum protein aggregates under similar culture conditions. 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. In conclusion, we have developed a novel noninvasive diagnostic and predictive assay for AD, MCI and PE.