Abstract
BACKGROUND: 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 inflammatory inducers and precise innate signaling pathway contributing to AD pathology remain largely undefined. RESULTS: In 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. CONCLUSION: These findings suggest that RIG-1 may play a critical role in incipient AD.