tRNA-derived RNA Fragments (tRF) as Prognostic and Diagnostic Biomarkers for Alzheimer’s Disease
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Principal Investigator: Xiaoyong Bao Organization: UNIVERSITY OF TEXAS MED BR GALVESTON Fiscal Year: 2024 Award: $799,998 Funding agency: National Institute on Aging PROJECT SUMMARY/ABSTRACT tRNA-derived RNA Fragments (tRFs), a newly discovered family of non-coding RNAs (ncRNAs), are emerging as essential disease biomarkers and regulators. Our recent publication demonstrated that tRFs are the most impacted small ncRNAs (sncRNAs) by Alzheimer's disease (AD) in the hippocampus. The changes are mainly from five tRFs, with one proven to correlate with the disease severity of AD experimentally. The correlation between an AD-impacted tRF and AD severity was also present in serum samples , supporting tRFs as promising AD indicators and potential prognostic/diagnostic biomarkers. Herein, we propose exploring a combination of an unbiased discovery method and a newly developed biomedical quantification approach to investigate whether the expression level of tRFs in the peripheral serum reflects the onset and progress of AD. During the discovery R61 phase, we will determine the clinical reliability of serum biomarkers to differentiate AD subjects from healthy individuals or individuals with non-AD dementia or non-dementia neurodegenerative diseases (Aim 1). We will then determine the lead tRF signatures or signature compositions and investigate the correlation between their changes with AD severity (Aim 2). The studies of the R61 phase will be mainly cross-sectional. During the R33 phase, we will investigate whether the AD biomarkers and their quantification assay can distinguish AD from its early mild cognitive impairment (MCI) stage. We will determine biomarker changes in disease progression in patients between baseline and subsequent follow-up patient visits. The patients who are healthy or have stable MCI over the years will be used as controls. The culmination of these aims will benefit both prognosis and diagnosis of AD. The feasibility of this approach is established by sample availability and our extensive research experience in tRFs and clinical service experience in AD. The overall goal of our research is to discover AD molecular biomarkers that could improve AD prevention and diagnosis and monitor the therapeutic efficacy in the future. 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Reticuloendothelial System><Blood Serum><Body Tissues><Brain><Brain Nervous System><Cerebrospinal Fluid><Clinical><Clinical Evaluation><Clinical Services><Clinical Testing><Cognitive><Cognitive Retention Disorders><Cornu Ammonis><Data><Degenerative Neurologic Disorders><Dementia><Development><Disease><Disease Progression><Disorder><Encephalon><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Evaluation><FDG PET><Family><Functional RNA><Future><Gehrig's Disease><Genes><Goals><Hippocampus><Human><Individual><Lead><Longitudinal Studies><Lou Gehrig Disease><MT-bound tau><Machine Learning><Memory Disorders><Memory Loss><Methods><Micro RNA><MicroRNAs><Modality><Modern Man><Monitor><National Institute of Aging><National Institute on Aging><Nerve Degeneration><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Neuron Degeneration><Neuropsychologies><Neuropsychology><Non-Coding><Non-Coding RNA><Non-Polyadenylated RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><PET><PET Scan><PET imaging><PETSCAN><PETT><Paralysis Agitans><Parents><Parkinson><Parkinson Disease><Patients><Pb element><Peripheral><Persons><Phase><Plasma><Plasma Serum><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prevention><Primary Parkinsonism><Primary Senile Degenerative Dementia><Process><Prognosis><Prognostic Marker><Publications><Qualifying><Quantitative RTPCR><Quantitative Reverse Transcriptase PCR><RNA><RNA Gene Products><RNA Nucleases><RNA Seq><RNA sequencing><RNAseq><RNase><Rad.-PET><Reporting><Research><Reticuloendothelial System, Serum, Plasma><Ribonuclease Family Protein><Ribonucleases><Ribonucleic Acid><Role><Sampling><Scanning><Scientific Publication><Screening procedure><Serum><Severity of illness><Small 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dementia><noncoding><novel><novel diagnostics><p-tau><p-τ><parent><patient living with Alzheimer's disease><patient suffering from Alzheimer's disease><patient with Alzheimer's><patient with Alzheimer's disease><phospho-tau><phospho-τ><phosphorylated tau><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><post-translational modification of tau><posttranslational modification of tau><pre-clinical><preclinical><primary degenerative dementia><prognostic><prognostic biomarker><qRTPCR><research clinical testing><screening tools><senile dementia of the Alzheimer type><skills><social role><spinal fluid><tRNA><tau><tau Proteins><tau factor><tau phosphorylation><tau posttranslational modification><tau-1><therapeutic efficacy><therapy efficacy><transcriptional differences><transcriptome sequencing><transcriptomic sequencing><transfer Ribonucleic acids><translation research><translational investigation><τ Proteins><τ phosphorylation>