Brain messenger RNA levels and ribonuclease activity in Alzheimer's disease

1987 ◽  
Vol 15 (1) ◽  
pp. 133-134 ◽  
Author(s):  
M. R. MORRISON ◽  
S. PARDUE ◽  
K. MASCHOFF ◽  
W. S. T. GRIFFIN ◽  
C. L. WHITE ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Messenger Rna ◽  
Ribonuclease Activity ◽  
Rna Levels

scholarly journals Lithium alters expression of RNAs in a type-specific manner in differentiated human neuroblastoma neuronal cultures, including specific genes involved in Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bryan Maloney ◽  
Yokesh Balaraman ◽  
Yunlong Liu ◽  
Nipun Chopra ◽  
Howard J. Edenberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bipolar Disorders ◽  
Sequence Length ◽  
Neuronal Cultures ◽  
Human Neuroblastoma ◽  
Protein Coding ◽  
Whole Transcriptome ◽  
Nucleolar Rnas ◽  
Rna Levels

AbstractLithium (Li) is a medication long-used to treat bipolar disorder. It is currently under investigation for multiple nervous system disorders, including Alzheimer’s disease (AD). While perturbation of RNA levels by Li has been previously reported, its effects on the whole transcriptome has been given little attention. We, therefore, sought to determine comprehensive effects of Li treatment on RNA levels. We cultured and differentiated human neuroblastoma (SK-N-SH) cells to neuronal cells with all-trans retinoic acid (ATRA). We exposed cultures for one week to lithium chloride or distilled water, extracted total RNA, depleted ribosomal RNA and performed whole-transcriptome RT-sequencing. We analyzed results by RNA length and type. We further analyzed expression and protein interaction networks between selected Li-altered protein-coding RNAs and common AD-associated gene products. Lithium changed expression of RNAs in both non-specific (inverse to sequence length) and specific (according to RNA type) fashions. The non-coding small nucleolar RNAs (snoRNAs) were subject to the greatest length-adjusted Li influence. When RNA length effects were taken into account, microRNAs as a group were significantly less likely to have had levels altered by Li treatment. Notably, several Li-influenced protein-coding RNAs were co-expressed or produced proteins that interacted with several common AD-associated genes and proteins. Lithium’s modification of RNA levels depends on both RNA length and type. Li activity on snoRNA levels may pertain to bipolar disorders while Li modification of protein coding RNAs may be relevant to AD.

Selective messenger RNA reduction in Alzheimer's disease

1988 ◽  
Vol 3 (3) ◽  
pp. 255-261 ◽  
Author(s):  
D.R.Crapper Mclachlan ◽  
W.J. Lukiw ◽  
L. Wong ◽  
C. Bergeron ◽  
N.T. Bech-Hansen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Messenger Rna

scholarly journals Predicting Clinical Dementia Rating Using Blood RNA Levels

2019 ◽  
Author(s):  
Justin B. Miller ◽  
John S.K. Kauwe ◽  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microarray Data ◽  
Predictive Accuracy ◽  
Cognitive Status ◽  
Clinical Dementia Rating ◽  
P Values ◽  
Intracellular Channel ◽  
Rna Levels

Structured AbstractINTRODUCTIONThe Clinical Dementia Rating (CDR) is commonly used to assess cognitive decline in Alzheimer’s disease patients.METHODSWe divided 741 participants with blood microarray data in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) into three groups based on their most recent CDR assessment: cognitive normal (CDR=0), mild dementia (CDR=0.5), and probable AD (CDR≥1.0). We then used machine learning to predict cognitive status using only blood RNA levels.RESULTSOne chloride intracellular channel 1 (CLIC1) probe was significant. By combining nonsignificant probes with p-values less than 0.1, we averaged 87.87 (s = 1.02)% predictive accuracy in classifying the three groups, compared to a 55.46% baseline for this study.DISCUSSIONWe identified one significant probe in CLIC1. However, CLIC1 levels alone were not sufficient to determine dementia status. We propose that combining individually suggestive, but nonsignificant, blood RNA levels can significantly improve diagnostic accuracy.

scholarly journals Differential blood miRNA expression in brain amyloid imaging defined Alzheimer's disease and controls.

2019 ◽  
Author(s):  
Helen Zong Ying Wu ◽  
Anbupalam Thalamuthu ◽  
Lesley Cheng ◽  
Christopher Fowler ◽  
Colin L Masters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mirna Expression ◽  
Messenger Rna ◽  
Amyloid Imaging ◽  
Imaging Biomarkers ◽  
Small Rna Sequencing ◽  
Amyloid Burden ◽  
Imaging Results ◽  
Study Results

Abstract Background: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging defined AD and normal cognition. Methods: Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher’s exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function. Results: After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p<0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle respectively, both of which have relevance to AD pathogenesis. Conclusion: Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility.

scholarly journals Inflamma-MicroRNAs in Alzheimer’s Disease: From Disease Pathogenesis to Therapeutic Potentials

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuanyuan Liang ◽  
Lin Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Messenger Rna ◽  
Senile Dementia ◽  
Therapeutic Targets ◽  
Peripheral Circulation ◽  
Diagnostic Biomarkers ◽  
Non Coding Rnas ◽  
Shed Light

Alzheimer’s disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3′ untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.

Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease

1991 ◽  
Vol 21 (4) ◽  
pp. 855-866 ◽  
Author(s):  
Paul J. Harrison ◽  
Amanda J. L. Barton ◽  
Abdolrahman Najlerahim ◽  
Brendan McDonald ◽  
R. Carl A. Pearson
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Messenger Rna ◽  
Pyramidal Neurons ◽  
Temporal Cortex ◽  
Granule Cell Layer ◽  
Brain Gene Expression ◽  
Mrna Content ◽  
Functionally Impaired

SYNOPSISMessenger RNA (mRNA) is the key intermediate in the gene expression pathway. The amount of mRNA in Alzheimer's disease (AD) brains has been determined using in situ hybridization histochemistry (ISHH) to detect the poly(A) tails of polyadenylated mRNA (poly(A) + mRNA). On a regional basis, AD cases had significantly less poly(A) + mRNA than controls in hippocampus (field CA3) and cerebellum (granule cell layer). Analysis of constituent pyramidal neurons showed mean reductions per cell within AD hippocampus (field CA3) and temporal cortex, but not in visual cortex. Similar changes were seen in a small group of non-AD dementias. The finding of reduced poly(A) + mRNA content is another indication of the altered brain gene expression occurring in AD. It is proposed that measurement of poly(A) + mRNA may be valuable in identifying functionally impaired neuronal populations. The methodology also provides a means by which changes in the quantitative distribution of individual mRNAs can be determined relative to that of poly(A) + mRNA as a whole.

scholarly journals Microarray Profile of Long Noncoding RNA and Messenger RNA Expression in a Model of Alzheimer’s Disease

Life ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 64
Author(s):  
Linlin Wang ◽  
Li Zeng ◽  
Hailun Jiang ◽  
Zhuorong Li ◽  
Rui Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Skills ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Model Of Alzheimer’S Disease ◽  
Conserved Genes ◽  
Novel Biomarkers ◽  
The Brain ◽  
Ad Mouse Model

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by a deficiency in cognitive skills. Although long noncoding RNAs (lncRNAs) have been proposed as associated with AD, the aberrant lncRNAs expression and the co-expression of lncRNAs-mRNAs network in AD remains unclear. Therefore, in this study, lncRNA microarray was performed on the brain of APP/PS1 mice at different age, widely used as an AD mouse model, and on age-matched wide-type controls. Our results identified a total of 3306 lncRNAs and 2458 mRNAs as aberrantly expressed among AD mice at different age and their age-matched control. Gene Ontology and pathway analysis of the AD-related lncRNAs and mRNAs indicated that neuroinflammation-related and synaptic transmission signaling pathways represented the main enriched pathways. An lncRNA–mRNA–miRNA network between the differentially expressed transcripts was constructed. Moreover, an mRNA–miRNA network between both significantly dysregulated and highly conserved genes was also constructed, and among this network, the IGF1, P2RX7, TSPO, SERPINE1, EGFR, HMOX1, and NFE212 genes were predicted to play a role in the development of AD. In conclusion, this study illustrated the prognostic value of lncRNAs and mRNAs associated to AD pathology by microarray analysis and might provide potential novel biomarkers in the diagnosis and treatment of AD.

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