This paper was aimed to analyze the microRNA (miRNA) signatures in Alzheimer disease (AD) and find the significant expressions of miRNAs, their target genes, the functional enrichment analysis of the confirmed genes, and potential drug treatment. The miRNA expression information of the gene expression profile data was downloaded from the Gene Expression Omnibus database. The total data sample size is 1309, including 1021 AD samples and 288 normal samples. A total of 21 differentially expressed miRNAs were obtained, of which 16 (hsa-miR-6761-3p, hsa-miR-6747-3p, hsa-miR-6875-3p, hsa-miR-6754-3p, hsa-miR-6736-3p, hsa-miR-6762-3p, hsa-miR-6787-3p, hsa-miR-208a-5p, hsa-miR-6740-3p, hsa-miR-6778-3p, hsa-miR-595, hsa-miR-6753-3p, hsa-miR-4747-3p, hsa-miR-3646, hsa-miR-6716-3p and hsa-miR-4435) were up-regulated and 5 (hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131 and hsa-miR-125b-1-3p) were down-regulated in AD. A total of 6 miRNAs (hsa-miR-595, hsa-miR-3646, hsa-miR-4435 hsa-miR-125a-3p, hsa-miR-22-3p and hsa-miR-24-3p) and 78 miRNA-disease-related gene sub-networks were predicted, and 116 ceRNA regulatory relationship pairs, and the ceRNA regulatory network were obtained. The results of enrichment analysis suggested that the main target pathways of several miRNAs differentially expressed in AD were mitogen-activated protein kinase signal pathway. According to the prediction results of Drug-Gene Interaction database 2.0, we obtained 53 pairs of drug-gene interaction, including 7 genes (PTGS2, EGFR, CALM1, PDE4D, FGFR2, HMGCR, cdk6) and 53 drugs. We hope our results are helpful to find a viable way to prevent, delay the onset, diagnose, and treat AD.

Background: Many studies have reported on the role of statin therapy in dementia, but its efficacy remains controversial. We aimed to search for reliable and meaningful articles to assess the efficacy of statin therapy for dementia risk, cognitive items, and pathologic markers. Methods: Related literature for this study was published in the period from January 1, 1987 to January 1, 2018. Odds ratio (OR) and 95% confidence interval (95% CI) estimates were pooled in either fixed or random effects models. Results: A total of 23 relevant studies were included after the application of the search strategy. The pooled results showed that statin therapy would downregulate dementia risk according to an analysis of 1,314,431 dementia patients and 1,836,539 healthy controls (OR: 0.64, 95% CI: 0.50, 0.81). In addition, specific changes in mini-mental state examination (MMSE) score were observed in individuals with dementia with statin therapy (OR: 0.46, 95% CI: 0.17, 0.74). However, the results of this meta-analysis showed that statin therapy did not significantly modify the Alzheimer’s Disease Assessment Scale (ADAS-cog) score (OR: −0.26, 95% CI: −1.13, 0.62). No significant association was found between statin therapy and activities of daily living performance (OR: −0.69, 95% CI: −4.12, 2.74). When investigating pathological markers, our results indicated a significant influence of statin therapy on plasma amyloid β₄₀ (Aβ₄₀) (OR: 9.27, 95% CI: 0.71, 17.84), plasma Aβ₄₂ (OR: 2.60, 95% CI: 1.07, 4.13), plasma low-density lipoprotein (LDL) cholesterol (OR: −16.95, 95% CI: −25.54, −8.37), plasma lathosterol (OR: −0.11, 95% CI: −0.14, −0.07), plasma 24s-hydroxycholesterol (OR: −10.41, 95% CI: −15.57, −5.25), and cerebrospinal fluid (CSF) lathosterol (OR: −0.07, 95% CI: −0.12, −0.01). Conclusions: The available data indicate that statin therapy may reduce dementia risk, altering cognitive items and pathologic markers.

Background: The complement component (3b/4b) receptor 1 gene (CR1) gene has been proved to affect the susceptibility of Alzheimer’s disease (AD) in different ethnic and districts groups. However, the effect of CR1 genetic variants on amyloid β (Aβ) metabolism of AD human is still unclear. Hence, the aim of this study was to investigate genetic influences of CR1 gene on Aβ metabolism. Methods: All data of AD patients and normal controls (NC) were obtained from alzheimer’s disease neuroimaging initiative database (ADNI) database. In order to assess the effect of each single nucleotide polymorphism (SNP) of CR1 on Aβ metabolism, the PLINK software was used to conduct the quality control procedures to enroll appropriate SNPs. Moreover, the correlation between CR1 genotypes and Aβ metabolism in all participants were estimated with multiple linear regression models. Results: After quality control procedures, a total of 329 samples and 83 SNPs were enrolled in our study. Moreover, our results identified five SNPs (rs10494884, rs11118322, rs1323721, rs17259045 and rs41308433), which were linked to Aβ accumulation in brain. In further analyses, rs17259045 was found to decrease Aβ accumulation among AD patients. Additionally, our study revealed the genetic variants in rs12567945 could increase CSF Aβ₄₂ in NC population. Conclusions: Our study had revealed several novel SNPs in CR1 genes which might be involved in the progression of AD via regulating Aβ accumulation. These findings will provide a new basis for the diagnosis and treatment AD.

Complement component (3b/4b) receptor 1 (CR1) expression is positively related to the abundance of phosphorylated microtubule-associated protein tau (tau), and CR1 expression is associated with susceptibility to Alzheimer's disease. However, the exact role of CR1 in tau protein-associated neurodegenerative diseases is unknown. In this study, we show that the mouse Cr1-related protein Y (Crry) gene, Crry, is localized to microglia. We also found that Crry protein expression in the hippocampus and cortex was significantly elevated in P301S mice (a mouse model widely used for investigating tau pathology) compared with that in wild-type mice. Tau protein phosphorylation (at serine 202, threonine 205, threonine 231, and serine 262) and expression of the major tau kinases glycogen synthase kinase-3 beta and cyclin-dependent-like kinase 5 were greater in P301S mice than in wild-type mice. Crry silencing by lentivirus-transfected short hairpin RNA led to greatly reduced tau phosphorylation and glycogen synthase kinase-3 beta and cyclin-dependent-like kinase 5 activity. Crry silencing reduced neuronal apoptosis and rescued cognitive impairment of P301S mice. Crry silencing also reduced the levels of the neuroinflammatory factors interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and the complement components complement 3 and complement component 3b. Our results suggest that Crry silencing in the P301S mouse model reduces tau protein phosphorylation by reducing the levels of neuroinflammation and complement components, thereby improving cognitive function.