P2-279: CSF SMALL RNA BIOMARKERS FOR ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_14) ◽  
pp. P785-P786
Author(s):  
Yuk Yee Leung ◽  
Yi-Fan Chou ◽  
Steven E. Arnold ◽  
John Q. Trojanowski ◽  
Gerard D. Schellenberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Rna ◽  
Rna Biomarkers

scholarly journals MicroRNA-Seq Data Analysis Pipeline to Identify Blood Biomarkers for Alzheimer's Disease from Public Data

2015 ◽  
Vol 10 ◽  
pp. BMI.S25132 ◽  
Author(s):  
Jun-ichi Satoh ◽  
Yoshihiro Kino ◽  
Shumpei Niida
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Data Analysis ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Analysis Pipeline ◽  
Web Based ◽  
Public Data ◽  
Data Analysis Pipeline

Background Alzheimer's disease (AD) is the most common cause of dementia with no curative therapy currently available. Establishment of sensitive and non-invasive biomarkers that promote an early diagnosis of AD is crucial for the effective administration of disease-modifying drugs. MicroRNAs (miRNAs) mediate posttranscriptional repression of numerous target genes. Aberrant regulation of miRNA expression is implicated in AD pathogenesis, and circulating miRNAs serve as potential biomarkers for AD. However, data analysis of numerous AD-specific miRNAs derived from small RNA-sequencing (RNA-Seq) is most often laborious. Methods To identify circulating miRNA biomarkers for AD, we reanalyzed a publicly available small RNA-Seq dataset, composed of blood samples derived from 48 AD patients and 22 normal control (NC) subjects, by a simple web-based miRNA data analysis pipeline that combines omiRas and DIANA miRPath. Results By using omiRas, we identified 27 miRNAs expressed differentially between both groups, including upregulation in AD of miR-26b-3p, miR-28–3p, miR-30c-5p, miR-30d-5p, miR-148b-5p, miR-151a-3p, miR-186–5p, miR-425–5p, miR-550a-5p, miR-1468, miR-4781–3p, miR-5001–3p, and miR-6513–3p and downregulation in AD of let-7a-5p, let-7e-5p, let-7f-5p, let-7g-5p, miR-15a-5p, miR-17–3p, miR-29b-3p, miR-98–5p, miR-144–5p, miR-148a-3p, miR-502–3p, miR-660–5p, miR-1294, and miR-3200–3p. DIANA miRPath indicated that miRNA-regulated pathways potentially down– regulated in AD are linked with neuronal synaptic functions, while those upregulated in AD are implicated in cell survival and cellular communication. Conclusions The simple web-based miRNA data analysis pipeline helps us to effortlessly identify candidates for miRNA biomarkers and pathways of AD from the complex small RNA–Seq data.

scholarly journals Relationships of Alzheimer’s disease and apolipoprotein E genotypes with small RNA and protein cargo of brain tissue extracellular vesicles

2020 ◽  
Author(s):  
Yiyao Huang ◽  
Tom A. P. Driedonks ◽  
Lesley Cheng ◽  
Andrey Turchinovich ◽  
Harinda Rajapaksha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Small Rna ◽  
Apoe Genotype ◽  
Tau Proteins ◽  
Small Rna Sequencing ◽  
Health Crisis ◽  
Metabolic Functions ◽  
Apolipoprotein E Genotypes

ABSTRACTAlzheimer’s disease (AD) is a public health crisis that grows as populations age. Hallmarks of this neurodegenerative disease include aggregation of beta-amyloid peptides and hyperphosphorylated tau proteins in the brain. Variants of the APOE gene are the greatest known risk factors for sporadic AD. As emerging players in AD pathophysiology, extracellular vesicles (EVs) contain proteins, lipids, and RNAs and are involved in disposal of cellular toxins and intercellular communication. AD-related changes in the molecular composition of EVs may contribute to pathophysiology and lend insights into disease mechanisms. We recently adapted a method for separation of brain-derived EVs (bdEVs) from post-mortem tissues. Using this method, we isolated bdEVs from AD patients with different APOE genotypes (n=23) and controls (n=7). bdEVs were counted, sized, and subjected to parallel small RNA sequencing and proteomic analysis. Numerous bdEV-associated RNAs and proteins correlated with AD pathology and APOE genotype. Some of the identified entities have been implicated previously in important AD-related pathways, including amyloid processing, neurodegeneration, and metabolic functions. These findings provide further evidence that bdEVs and their molecular cargo modulate development and progression of AD.

scholarly journals Small RNA modifications in Alzheimer’s disease

2020 ◽  
Author(s):  
Xudong Zhang ◽  
Fatima Trebak ◽  
Lucas AC Souza ◽  
Junchao Shi ◽  
Tong Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Prefrontal Cortex ◽  
Small Rna ◽  
Small Rnas ◽  
Post Mortem ◽  
Rna Modifications ◽  
Non Coding Rnas ◽  
And Control

AbstractBackgroundWhile significant advances have been made in uncovering the aetiology of Alzheimer’s disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known.MethodsWe performed LC-MS/MS–based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer’s disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD).FindingsWe report altered small RNA modifications in AD samples compared with normal controls. The 15–25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30–40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30–40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg.InterpretationThese data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer’s disease.FundingNIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe.Research in ContextEvidence before this studyAlzheimer’s disease (AD) and vascular dementia (VaD) are marked by cognitive impairment and neuropathologies caused by significant neuronal death. Associated gene mutations are rare in subjects with dementia, and the aetiology of these diseases is still not completely understood. Recent emerging evidence suggests that epigenetic changes are risk factors for the development of dementia. However, studies assessing small RNA modifications—one of the features of epigenetics—in dementia are lacking.Added value of this studyWe used high-throughput liquid chromatography-tandem mass spectrometry and small RNA sequencing to profile small RNA modifications and the composition of small RNAs in post-mortem samples of the prefrontal cortex of AD and control subjects. We detected and quantified 16 types of RNA modifications and identified distinct small non-coding RNAs and modification signatures in AD subjects compared with controls.Implications of all the available evidenceThis study identified novel types and compositions of small RNA modifications in the prefrontal cortex of AD patients compared with control subjects in post-mortem samples. The cellular locations of these RNA modifications and whether they are drivers or outcomes of AD are still not known. However, results from the present study may open new possibilities for dissecting the dementia pathology.

scholarly journals Small RNA fingerprinting of Alzheimer's disease frontal cortex extracellular vesicles and their comparison with peripheral extracellular vesicles

2020 ◽  
Vol 9 (1) ◽  
pp. 1766822 ◽  
Author(s):  
Lesley Cheng ◽  
Laura J. Vella ◽  
Kevin J. Barnham ◽  
Catriona McLean ◽  
Colin L. Masters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Cortex ◽  
Extracellular Vesicles ◽  
Small Rna ◽  
Rna Fingerprinting

scholarly journals Small RNA modifications in Alzheimer's disease

2020 ◽  
Vol 145 ◽  
pp. 105058
Author(s):  
Xudong Zhang ◽  
Fatima Trebak ◽  
Lucas A.C. Souza ◽  
Junchao Shi ◽  
Tong Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Rna ◽  
Rna Modifications

scholarly journals miR-186 in Alzheimer's disease: a big hope for a small RNA?

2016 ◽  
Vol 137 (3) ◽  
pp. 308-311 ◽  
Author(s):  
Saoussen Ben Halima ◽  
Gabriele Siegel ◽  
Lawrence Rajendran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Rna

Small RNA sequencing revealed dysregulated piRNAs in Alzheimer's disease and their probable role in pathogenesis

2017 ◽  
Vol 13 (3) ◽  
pp. 565-576 ◽  
Author(s):  
Jyoti Roy ◽  
Arijita Sarkar ◽  
Sibun Parida ◽  
Zhumur Ghosh ◽  
Bibekanand Mallick
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Rna Sequencing ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Healthy Human ◽  
Probable Role ◽  
First Time

For the first time, this study reports specific piRNA signatures in a healthy human brain and an AD-diagnosed brain and decrypted the regulatory roles of dysregulated piRNAs in the pathogenesis of AD.

Cognitive control constrains memory attributions

2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Control

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.

Formation of paired helical filaments in Alzheimer's disease

1984 ◽  
Vol 42 ◽  
pp. 302-303
Author(s):  
J. Metuzals ◽  
D. F. Clapin ◽  
V. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Lobe ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Normal Brain ◽  
Protein Assemblies ◽  
Electron Microscopic ◽  
Helical Symmetry ◽  
Structural Levels

Information on the conformation of paired helical filaments (PHF) and the neurofilamentous (NF) network is essential for an understanding of the mechanisms involved in the formation of the primary lesions of Alzheimer's disease (AD): tangles and plaques. The structural and chemical relationships between the NF and the PHF have to be clarified in order to discover the etiological factors of this disease. We are investigating by stereo electron microscopic and biochemical techniques frontal lobe biopsies from patients with AD and squid giant axon preparations. The helical nature of the lesion in AD is related to pathological alterations of basic properties of the nervous system due to the helical symmetry that exists at all hierarchic structural levels in the normal brain. Because of this helical symmetry of NF protein assemblies and PHF, the employment of structure reconstruction techniques to determine the conformation, particularly the handedness of these structures, is most promising. Figs. 1-3 are frontal lobe biopsies.

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