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.
Recent evidence has accumulated that Alzheimer’s disease (AD) is associated with a central nervous system (CNS) inflammatory response. Neuroinflammation is a complex response against harmful effects of diverse stimuli and plays a critical role in the pathogenesis of AD. An important arm of the inflammatory response is the innate immune response. The innate immune response is regulated by pattern recognition receptors (PRRs) and their signaling pathways. Here we report that the expression of the innate immune response proteins, retinoic acid-inducible gene-I (RIG-1), virus-induced signaling adaptor (VISA), and the NACHT leucine-rich domain and pyrin-containing protein, NLRP12 are significantly elevated in neurons of the temporal cortex, the cerebrospinal fluid and plasma in presymptomatic AD patients, post-mortem diagnosis. Increased expression of RIG-1 and VISA were not found in pathologically confirmed cases of amyotrophic lateral sclerosis, Diffuse Lewy Body disease or Huntington’s disease, suggesting that activation of RIG-1 signaling may be a specific marker for early AD pathogenesis. Moreover, in vitro results show that stimulation of RIG-1 signaling induces expression of amyloid precursor protein and β-amyloid, supporting the idea that activation of the RIG-1 signaling system occurs in presymptomatic AD.
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