Alzheimer’s disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Aβ clearance via CD36-mediated phagocytosis of Aβ in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1β and TNF-α, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.

The innate immune system plays key roles in controlling Alzheimer's disease (AD), while secreting cytokines to eliminate pathogens and regulating brain homeostasis. Recent research in the field of AD has shown that the innate immune-sensing ability of pattern recognition receptors on brain-resident macrophages, known as microglia, initiates neuroinflammation, Aβ accumulation, neuronal loss, and memory decline in patients with AD. Advancements in understanding the role of innate immunity in AD have laid a strong foundation to elucidate AD pathology and devise therapeutic strategies for AD in the future. In this review, we highlight the present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion in AD. We also discuss how the AD pathology influences these biological processes.

Alzheimer’s disease (AD), an age-dependent, progressive neurodegenerative disorder, is the most common type of dementia, accounting for 50–70% of all dementia cases. Due to the increasing incidence and corresponding socioeconomic burden of dementia, it has rapidly emerged as a challenge to public health worldwide. The characteristics of AD include the development of extracellular amyloid-beta plaques and intracellular neurofibrillary tangles, vascular changes, neuronal inflammation, and progressive brain atrophy. However, the complexity of the biology of AD has hindered progress in elucidating the underlying pathophysiological mechanisms of AD, and the development of effective treatments. MicroRNAs (miRNAs, which are endogenous, noncoding RNAs of approximately 22 nucleotides that function as posttranscriptional regulators of various genes) are attracting attention as powerful tools for studying the mechanisms of diseases, as they are involved in several biological processes and diseases, including AD. AD is a multifactorial disease, and several reports have suggested that miRNAs play an important role in the pathological processes of AD. In this review, the basic biology of miRNAs is described, and the function and physiology of miRNAs in the pathological processes of AD are highlighted. In addition, the limitations of current pharmaceutical therapies for the treatment of AD and the development of miRNA-based next-generation therapies are discussed.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-β (Aβ) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aβ deposition in the brain has not been observed. Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aβ positron emission tomography (Aβ-PET) positivity in patients with AD. Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive participants compared to Aβ-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive AD patients vs. Aβ-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aβ-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217. These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aβ deposition in the brain and had high diagnostic accuracy for predicting Aβ-PET positivity.

The effects of onion peel extract (OPE) in collagen (5 μg/mL)-stimulated washed rat platelet aggregation were investigated. OPE inhibited platelet aggregationviainhibition of aggregation-inducing molecules, intracellular Ca²⁺and thromboxane A₂(TXA₂) by blocking cyclooxygenase-1 (COX-1) and TXA₂synthase (TXAS) activities in a dose-dependent manner. In addition, OPE elevated the formation of cyclic adenosine monophosphate (cAMP), aggregation-inhibiting molecule, but not cyclic guanosine monophosphate (cGMP). High performance liquid chromatography (HPLC) analysis of OPE revealed that OPE contains quercetin, one of the major flavonoids, which has anti-platelet effect. In conclusion, we suggest that OPE is an effective inhibitor of collagen-stimulated platelet aggregationin vitro. Therefore, it can be a promising and safe strategy for anti-cardiovascular diseases.

Neurodegenerative diseases (NDDs) are age-related disorders characterized by progressive neurodegeneration and neuronal cell loss in the central nervous system. Neuropathological conditions such as the accumulation of misfolded proteins can cause neuroinflammation, apoptosis, and synaptic dysfunction in the brain, leading to the development of NDDs including Alzheimer’s disease (AD) and Parkinson’s disease (PD). MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression post-transcriptionally via RNA interference. Recently, some studies have reported that some miRNAs play an important role in the development of NDDs by regulating target gene expression. MiRNA-485 (miR-485) is a highly conserved brain-enriched miRNA. Accumulating clinical reports suggest that dysregulated miR-485 may be involved in the pathogenesis of AD and PD. Emerging studies have also shown that miR-485 plays a novel role in the regulation of neuroinflammation, apoptosis, and synaptic function in the pathogenesis of NDDs. In this review, we introduce the biological characteristics of miR-485, provide clinical evidence of the dysregulated miR-485 in NDDs, novel roles of miR-485 in neuropathological events, and discuss the potential of targeting miR-485 as a diagnostic and therapeutic marker for NDDs.