Identification of prefrontal cortex protein alterations in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia in developed countries. A better understanding of the events taking place at the molecular level would help to identify novel protein alterations, which might be used in diagnosis or for treatment development. In this study, we have performed the high-throughput analysis of 706 molecules mostly implicated in cell-cell communication and cell signaling processes by using two antibody microarray platforms.We screened three AD pathological groups -each one containing four pooled samples- from Braak stages IV, V and VI, and three control groups from two healthy subjects, five frontotemporal and two vascular dementia patients onto Panorama and L-Series antibody microarrays to identify AD-specific alterations not common to other dementias. Forty altered proteins between control and AD groups were detected, and validated by i) meta-analysis of mRNA alterations, ii) WB, and iii) FISH and IHC using an AD-specific tissue microarray containing 44 samples from AD patients at different Braak stages, and frontotemporal and vascular dementia patients and healthy individuals as controls.We identified altered proteins in AD not common to other dementias like the E3 ubiquitin-protein ligase TOPORS, Layilin and MICB, and validated the association to AD of the previously controverted proteins DDIT3 and the E3 ubiquitin-protein ligase XIAP. These altered proteins constitute interesting targets for further immunological analyses using sera, plasma and CSF to identify AD blood- or cerebrospinal fluid-biomarkers and to perform functional analysis to determine their specific role in AD, and their usefulness as potential therapeutic targets of intervention.

Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aβ1-42-Induced Rat Model of Alzheimer’s Disease

“…The prefrontal cortex (PFC) is implicated in cognitive processes including working memory, temporal processing, decision-making, flexibility, and goal-oriented behavior [9]. Alterations in prefrontal cortex (PFC) function and abnormalities in its interactions with other brain areas (i.e., the hippocampus) have been related to Alzheimer's disease (AD) [10]. Several potential biomarkers have been proposed for preclinical AD and are mainly related to lipid metabolism.…”

Investigating LGALS3BP/90 K glycoprotein in the cerebrospinal fluid of patients with neurological diseases

“…The value in the CSF is about 1 to 2 orders of magnitude lower than that reported for serum using the same ELISA assay (healthy controls: 5.4 mg/l; supplier datasheet) or using an MRM assay (cognitive healthy controls: 24 mg/l 14 ). 90 K has been found in brain tissue, e.g., an increase has been reported in the prefrontal cortex of Alzheimer's disease patients 29 but the expression levels in the brain are low comparatively to other tissues as described in The Human Protein Atlas 30 . Therefore, it is likely that 90 K from the CSF derives not only from brain tissue but also from the serum upon transfer via the blood-CSF barrier.…”

Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis

“…Identified proteins appearing in more than 10% of agarose-based immunoprecipitation experiments reported in CRAPome (Contaminant Repository for Affinity Purification Mass Spectrometry Data) data base were considered false positives [13]. Bioinformatics analysis of proteins passing this criterion was performed using STRING and IPA Analysis (Ingenuity Systems) to identify altered networks and pathways [14]. STRING Version 9.1 and MCL clustering enrichment 2 with the default 0.4 confidence score were used to identify the interacting partners in the dataset.…”

“…Core tumor tissue samples from 50 metastatic and non-metastatic CRC patients and core tumor tissue samples from 94 recurrent or non-recurrent CRC stage II patients composed the two TMAs used in the study. Immunohistochemical staining using optimized antibody dilutions (Supplementary Table S4), visualization and immunoreactivity was conducted according to established protocols [4,14,25,27].…”