Identification of prefrontal cortex protein alterations in Alzheimer's disease

• Published in: Oncotarget Vol. 9; no. 13; pp. 10847 - 10867
• Main Authors: Garranzo-Asensio, Maria, San Segundo-Acosta, Pablo, Martínez-Useros, Javier, Montero-Calle, Ana, Fernández-Aceñero, María Jesús, Häggmark-Månberg, Anna, Pelaez-Garcia, Alberto, Villalba, Mayte, Rabano, Alberto, Nilsson, Peter, Barderas, Rodrigo
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 16.02.2018
• Subjects: aged; alpha2 glycoprotein; Alzheimer disease; Alzheimer's disease; Bruton tyrosine kinase; BTK gene; CD36 antigen; chromogranin A; clinical article; controlled study; down regulation; female; ferritin; ferritin light chain; fluorescence in situ hybridization; frontotemporal dementia; furin; galectin 3; galectin 3 binding protein; gene; Gerotarget/Aging; growth arrest and DNA damage inducible protein 153; high throughput sequencing; human; human tissue; immunohistochemistry; KLK7 gene; Layilin; male; mannose binding lectin 2; messenger RNA; MHC class I polypeptide related sequence B; mRNA expression level; multiinfarct dementia; NELL2 gene; Neurodegeneration; prefrontal cortex; protein analysis; protein expression; protein kinase C; Protein/antibody microarrays; Proteomics; Research Paper: Gerotarget (Focus on Aging); signal transduction; somatostatin receptor 2; stratum corneum chymotryptic enzyme; stress activated protein kinase 1; synexin; tau protein; tissue microarray; ubiquitin protein ligase E3; ubiquitin protein ligase TOPORS; unclassified drug; upregulation; very elderly; Western blotting; X linked inhibitor of apoptosis; zinc alpha 2 glycoprotein; neurodegeneration; Alzheimer’s disease; proteomics; protein/antibody microarrays; Gerotarget/Aging
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.24303

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.