RIG-1 receptor expression in the pathology of Alzheimer’s disease

Juan Pablo De Rivero Vaccari,Deborah C Mash,W Dalton Dietrich,Christina Sedaghat,Robert W Keane,Frank J Brand

doi:10.1186/1742-2094-11-67

Juan Pablo De Rivero Vaccari, Deborah C Mash + Show 4 more

Open Access

https://doi.org/10.1186/1742-2094-11-67

Copy DOI

Abstract

BackgroundNeuroinflammation plays a critical role in the pathogenesis of Alzheimer’s disease (AD) and involves activation of the innate immune response via recognition of diverse stimuli by pattern recognition receptors (PRRs). The inflammatory inducers and precise innate signaling pathway contributing to AD pathology remain largely undefined.ResultsIn the present study we analyzed expression levels of innate immune proteins in temporal and occipital cortices from preclinical (no cognitive impairment, NCI, N = 22) to mild cognitive impairment (MCI, N = 20) associated with AD pathology (N = 20) and AD patients (N = 23). We found that retinoic acid-inducible gene-I (RIG-1) is significantly elevated in the temporal cortex and plasma in patients with MCI. In addition, primary human astrocytes stimulated with the RIG-1 ligand 5′ppp RNA showed increased expression of amyloid precursor protein (APP) and amyloid-β (Aβ), supporting the idea that RIG-1 is involved in the pathology of MCI associated with early progression to AD.ConclusionThese findings suggest that RIG-1 may play a critical role in incipient AD.

Highlights

Neuroinflammation plays a critical role in the pathogenesis of Alzheimer’s disease (AD) and involves activation of the innate immune response via recognition of diverse stimuli by pattern recognition receptors (PRRs)
The levels of retinoic acid-inducible gene-I (RIG-1) in the occipital cortex were higher in the AD group than in the no cognitive impairment (NCI) and mild cognitive impairment (MCI) groups (Figure 1C)
The results of the present study demonstrate that RIG-1 is significantly elevated in the plasma and temporal cortex of MCI patients with AD pathology whereas RIG1 is elevated in the occipital cortex of AD patients

Summary

Introduction

Neuroinflammation plays a critical role in the pathogenesis of Alzheimer’s disease (AD) and involves activation of the innate immune response via recognition of diverse stimuli by pattern recognition receptors (PRRs). Alzheimer’s disease (AD) pathogenesis is associated with central nervous system (CNS) inflammatory responses [1,2,3,4]. Amyloid-β (Aβ) fibrils trigger inflammatory responses mediated by Toll-like receptors (TLR)4/TLR6 in the presence of CD36 [1,2,3,4]. A polymorphism in the TLR4 extracellular domain has been reported to be associated with protection against late-onset AD in an Italian population [5], suggesting that a sterile inflammatory response could influence AD pathology through TLR4 signaling.

Methods

Results

Discussion

Conclusion