Identification of prefrontal cortex protein alterations in Alzheimer's Disease

• 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 fluidbiomarkers and to perform functional analysis to determine their specific role in AD, and their usefulness as potential therapeutic targets of intervention.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

Gerotarget/Aging

Neurodegeneration

Protein/antibody microarrays

Proteomics

alpha2 glycoprotein

Bruton tyrosine kinase

CD36 antigen

chromogranin A

ferritin

ferritin light chain

furin

galectin 3

galectin 3 binding protein

growth arrest and DNA damage inducible protein 153

Layilin

mannose binding lectin 2

messenger RNA

MHC class I polypeptide related sequence B

protein kinase C

somatostatin receptor 2

stratum corneum chymotryptic enzyme

stress activated protein kinase 1

synexin

tau protein

ubiquitin protein ligase E3

ubiquitin protein ligase TOPORS

unclassified drug

X linked inhibitor of apoptosis

zinc alpha 2 glycoprotein

aged

Alzheimer disease

Article

BTK gene

clinical article

controlled study

down regulation

female

fluorescence in situ hybridization

frontotemporal dementia

gene

high throughput sequencing

human

human tissue

immunohistochemistry

KLK7 gene

male

mRNA expression level

multiinfarct dementia

NELL2 gene

prefrontal cortex

protein analysis

protein expression

signal transduction

tissue microarray

upregulation

very elderly

Western blotting

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)