Profiling of long non-coding RNAs in hippocampal-entorhinal system subfields: impact of RN7SL1 on neuroimmune response modulation in Alzheimer's disease.

Alzheimer's disease (AD) is recognized as the predominant cause of dementia, and neuroimmune processes play a pivotal role in its pathological progression. The involvement of long non-coding RNAs (lncRNAs) in AD has attracted widespread attention. Herein, transcriptomic analysis of 262 unique samples extracted from five hippocampal-entorhinal system subfields of individuals with AD pathology and without AD pathology revealed distinctive lncRNA expression profiles. Through differential expression and coexpression analyses, we identified 16 pivotal lncRNAs. Notably, RN7SL1 knockdown significantly modulated microglial responses upon oligomeric amyloid-ß stimulation, resulting in a considerable decrease in proinflammatory cytokine production and subsequent neuronal damage. These findings highlight RN7SL1 as an essential neuroimmune-related lncRNA that could serve as a prospective target for AD diagnosis and treatment.

[Autosomal dominant intellectual disability-40 caused by a de novo mutation of the CHAMP1 gene: a case report].

A boy, aged 6 months, had the manifestations of intellectual and motor developmental delay, head instability, general weakness, unawareness of grasping objects by hands, and unusual facies (slightly wide eye distance, epicanthus, esotropia, mouth-opening appearance, short philtrum, and low-set ears). Gene detection results showed a de novo heterozygous frameshift mutation of the CHAMP1 gene at the chromosomal location of chr13:115089847, and nuclear acid was changed to c.530delCinsTTT, resulting in a change in amino acid to p.S177Ffs*2. Therefore, the boy was diagnosed with autosomal dominant intellectual disability-40 caused by the mutation in the CHAMP1 gene. This case report suggests that for children with unexplained intellectual disability, especially those with generalized hypotonia and severe language disorder, the possibility of CHAMP1 gene mutation should be considered, and genetic testing should be performed as early as possible.

[Clinical effectiveness of Subjective Global Nutritional Assessment in hospitalized children with cerebral palsy].

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS: There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.

Long RNA Profiles of Human Brain Extracellular Vesicles Provide New Insights into the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Extracellular vesicles (EVs), carriers of nucleic acids, lipids, and proteins, are known to play significant roles in neurodegenerative pathogenesis. Studies have shown that EVs from AD human brain tissue contain toxic proteins that may lead to neuron cell damage and loss. However, the potential contribution of EV long RNAs (exLR) to AD pathobiology is less well known, and their biochemical functions and molecular properties remain obscure. Here, EVs were isolated from the frontal cortex of normal control (NC; N = 10) and AD (N = 8) brain tissue donors. We performed exLR profiling on the isolated EVs followed by pathway analysis and weighted gene co-expression network analysis (WGCNA). A total of 1012 mRNAs, 320 long non-coding RNAs (lncRNAs), and 119 circular RNAs (circRNAs) were found to be differentially expressed (DE) in AD-EVs compared with NC-EVs. Functional analysis of the DEmRNAs revealed that metal ion transport, calcium signaling, and various neuronal processes were enriched. To investigate the possible functions of the identified DElncRNAs and DEcircRNAs, competing endogenous RNA (ceRNA) networks were constructed and subjected to WGCNA, in which two gene modules were identified to be significantly correlated with AD. Moreover, we discovered that NC-EVs were more effective than AD-EVs in promoting cytokine expression, phagocytosis, and induction of calcium signaling in microglia. Our study provides an in-depth characterization of brain tissue exLR and identifies several RNAs that correlate with the pathogenesis of AD.

Integrative Transcriptomic Analyses of Hippocampal-Entorhinal System Subfields Identify Key Regulators in Alzheimer's Disease.

The hippocampal-entorhinal system supports cognitive function and is selectively vulnerable to Alzheimer's disease (AD). Little is known about global transcriptomic changes in the hippocampal-entorhinal subfields during AD. Herein, large-scale transcriptomic analysis is performed in five hippocampal-entorhinal subfields of postmortem brain tissues (262 unique samples). Differentially expressed genes are assessed across subfields and disease states, and integrated genotype data from an AD genome-wide association study. An integrative gene network analysis of bulk and single-nucleus RNA sequencing (snRNA-Seq) data identifies genes with causative roles in AD progression. Using a system-biology approach, pathology-specific expression patterns for cell types are demonstrated, notably upregulation of the A1-reactive astrocyte signature in the entorhinal cortex (EC) during AD. SnRNA-Seq data show that PSAP signaling is involved in alterations of cell- communications in the EC during AD. Further experiments validate the key role of PSAP in inducing astrogliosis and an A1-like reactive astrocyte phenotype. In summary, this study reveals subfield-, cell type-, and AD pathology-specific changes and demonstrates PSAP as a potential therapeutic target in AD.