Level of LncRNA GAS5 and Hippocampal Volume are Associated with the Progression of Alzheimer’s Disease

Abstract

Purpose We evaluated the diagnostic value of long non-coding RNA growth arrest-specific transcript 5 (GAS5) and its relationship with hippocampal volume in Alzheimer’s disease (AD). Patients and Methods One hundred and eight patients with AD and 83 healthy controls were included, and demographic data, biochemical parameters, GAS5 levels, and hippocampal volume were recorded. Chi-squared tests or independent sample t-tests were used to compare the baseline characteristics, relative expression of GAS5, and hippocampal volume. Correlations between variables were determined using Spearman’s rank correlation test. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic value of GAS5 and total hippocampal volume in AD. Results The levels of GAS5 were significantly upregulated in patients with AD compared with those in controls and were negatively correlated with MMSE score. There were differences in left hippocampal volume, right hippocampal volume, and total hippocampal volume between the two groups. Total hippocampal volume was positively correlated with MMSE score and negatively correlated with GAS5 expression in patients with AD. The area under the curve (AUC) of for GAS5 expression was 0.831, the sensitivity was 61.1%, and the specificity was 95.2%. The AUC of the combined total hippocampal volume was 0.891, the sensitivity was 74.1%, and the specificity was 92.8%. Conclusion The results suggested that GAS5 may be an excellent indicator of AD progression alone or in combination with hippocampal volume.

Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model

“…Importantly, NPC86 binds to exon 12 which is highly conserved between mouse and human. Chen et al 71 analyzed PBMC from aged samples and reported that circulating GAS5 levels can be correlated to aging. We have shown that GAS5 is secreted in exosomes from cells, detected in serum and disease state can change the ratio of amount retained by cell versus secreted 72 .…”

Circulating long non-coding RNAs as novel diagnostic biomarkers for Alzheimer’s disease (AD): A systematic review and meta-analysis

“…GAS5 is an anti-oncogene extensively studied in tumors [ 33 ]. Cao and colleagues found that silencing GAS5 improved functional recovery, suppressed neuron cell apoptosis, and inhibited the inflammatory response in HT22 cells [ 47 ].…”

“…These findings suggested that GAS5 may be associated with the progression of AD. Interestingly, the expression of GAS5 was negatively correlated with hippocampal volume, suggesting that GAS5 may play an important regulatory role in hippocampal atrophy [ 33 ]. In contrast, Khodayi et al did not find a significant difference in GAS5-AS expression in plasma cells of AD patients compared with healthy controls [ 34 ].…”

“…The main characteristics of the seven studies included in the systematic review are summarized in Table 1. A total of 602 AD patients and 576 healthy controls from China [23,[30][31][32][33] and Iran [22,34] were included in the review. The main method for detecting lncRNAs in the included studies was Reverse Transcription and Quantitative Real-Time PCR (RT-qPCR).…”

“…Five studies reported sensitivity and specificity values of lncRNAs in diagnosing AD patients [22,[31][32][33][34]. Within these five studies, the above-mentioned parameters for five lncRNAs were reported.…”