miRNAs and Alzheimer’s Disease: Exploring the Role of Inflammation and Vitamin E in an Old-Age Population

Abstract

Alzheimer’s disease (AD) is the most frequent cause of dementia worldwide and represents one of the leading factors for severe disability in older persons. Although its etiology is not fully known yet, AD may develop due to multiple factors, including inflammation and oxidative stress, conditions where microRNAs (miRNAs) seem to play a pivotal role as a molecular switch. All these aspects may be modulated by nutritional factors. Among them, vitamin E has been widely studied in AD, given the plausibility of its various biological functions in influencing neurodegeneration. From a cohort of old-aged people, we measured eight vitamin E forms (tocopherols and tocotrienols), thirty cytokines/chemokines, and thirteen exosome-extracted miRNAs in plasma of subjects suffering from subjects affected by AD and age-matched healthy controls (HC). The sample population included 80 subjects (40 AD and 40 HC) with a mean age of 77.6 ± 3.8 years, mostly women (45; 56.2%). Of the vitamin E forms, only α-tocopherol differed between groups, with significantly lower levels in AD. Regarding the examined inflammatory molecules, G-CSF, GM-CSF, INF-α2, IL-3, and IL-8 were significantly higher and IL-17 lower in AD than HC. Among all miRNAs examined, AD showed downregulation of miR-9, miR-21, miR29-b, miR-122, and miR-132 compared to controls. MiR-122 positively and significantly correlated with some inflammatory molecules (GM-CSF, INF-α2, IL-1α, IL-8, and MIP-1β) as well as with α-tocopherol even after correction for age and gender. A final binary logistic regression analysis showed that α-tocopherol serum levels were associated with a higher AD probability and partially mediated by miR-122. Our results suggest an interplay between α-tocopherol, inflammatory molecules, and microRNAs in AD, where miR-122 may be a good candidate as modulating factor.

Qi-fu-yin attenuated cognitive disorders in 5xFAD mice of Alzheimer's disease animal model by regulating immunity

“…It is found that IL-17 is increased in APP/PS1 mice and Aβ-induced model mice and leads to neurotoxicity and cognitive decline through the IL-17/TRAF6/NF-κB pathway ( 53 ). However, the researchers found that the production of IL-17 in the 5xFAD mice decreased ( 54 ), and the level of IL-17 is also lower in AD patients ( 55 ), which is consistent with our research results. A study observed that IFN-γ levels in patients with mild and severe AD were higher than those in patients with moderate and MCI, respectively ( 56 ).…”

Comparative Insight into Microglia/Macrophages-Associated Pathways in Glioblastoma and Alzheimer’s Disease

“…From AD patient blood samples, AD showed downregulation of miR-9, miR-21, miR29-b, miR-122, and miR-132 compared to controls. Among these, miR-122 was positively and significantly correlated with several inflammatory factors including granulocyte-macrophage colony-stimulating factor (GM-CSF), INF-a2, IL-1a, IL-8, and major intrinsic protein-1p (MIP-1p) [ 65 ]. Moreover, in AD patient blood samples, miR-1908 levels were upregulated, but ApoE levels were reduced.…”

Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer’s Disease

“…Among patients with AD, upregulated levels of inflammatory markers and AD risk genes in association with innate immune functions have been unveiled, suggesting a prominent role of inflammation in the pathogenesis of AD [174]. The inflammatory process includes the activation of microglia and the production of pro-inflammatory cytokines [175]. Notably, microglial activation has been proven to be a vital factor linking the deleterious effects of Aβ to tau spread [176].…”