Weiming Xia
Boston University School of Medicine, U
Title: Combination of mass spectrometry-ELISA platforms for Alzheimer blood biomarkers
Biography
Biography: Weiming Xia
Abstract
Two pathological hallmarks of Alzheimer’s disease (AD) are Tau-containing neurofibrillary tangles and amyloid β protein (Aβ)-containing neuritic plaques. Due to the heterogeneity and multifactorial nature of AD, a single biomarker for diagnosis of AD has not been identified. In this study, we have collected peripheral blood mononuclear cells (PBMC) and plasma from AD patients and cognitive normal subjects. We have converted PBMC to induced pluripotent stem cell (iPSC) lines, and we have further differentiated iPSC into human 3D neurons. At autopsy, AD pathology was confirmed in brains of patients from whom we derived blood, iPSC and 3D neurons. Quantitation of Aβ and Tau by ELISA illustrated much higher levels of Aβ and phosphorylated Tau at residues Thr 181 and Thr 231 in brain tissue from superior and inferior frontal cortex area, compared to those from cerebellum region. Liquid chromatography/mass spectrometry was used to analyze plasma, iPSC, 3D neurons and post-mortem brain tissue labelled with isobaric mass tags for relative protein quantification. Our study revealed compartmental segregation as well as association of differentially expressed proteins between AD and control subjects. We found that the levels of Tau and neurofilament light and medium polypeptides were increased in 3D neurons derived from AD patients. Analysis of plasma samples also allows us to separate AD patients from healthy subjects. In conclusion, we present a unique platform to discover proteins linked to AD as candidate biomarkers.