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Oncotarget. 2018 Jan 24;9(13):10847-10867. doi: 10.18632/oncotarget.24303. eCollection 2018 Feb 16.

Identification of prefrontal cortex protein alterations in Alzheimer's disease.

Author information

1
Biochemistry and Molecular Biology Department I, Chemistry Faculty, Complutense University of Madrid, Madrid, Spain.
2
Translational Oncology Division, OncoHealth Institute, Fundacion Jimenez Diaz University Hospital, Madrid, Spain.
3
Servicio de Anatomía Patológica Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Departamento de Anatomía Patològica, Facultad de Medicina, Complutense University of Madrid, Madrid, Spain.
4
Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden.
5
Department of Pathology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
6
Alzheimer Disease Research Unit, CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, Spain.
7
UFIEC, National Institute of Health Carlos III, Majadahonda, Madrid, Spain.

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.

KEYWORDS:

Alzheimer’s disease; Gerotarget/Aging; neurodegeneration; protein/antibody microarrays; proteomics

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