TDP-43 pathology prevalence and distribution in AD cases

Exploratory Score: 0.800 Price: $0.50 Alzheimer's disease human postmortem brain tissue Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting TARDBP in human postmortem brain tissue. Primary outcome: prevalence and distribution of TDP-43 pathology

Description

Neuropathological examination of Alzheimer's disease cases to determine the prevalence and distribution pattern of TDP-43 inclusions. The study found that TDP-43 inclusions occur in up to 57% of AD cases, most commonly in a limbic distribution pattern, with or without associated hippocampal sclerosis. The inclusions consist of phosphorylated and truncated forms of TDP-43 protein forming cytoplasmic inclusion bodies. In some cases, TDP-43 deposits were observed co-localizing with neurofibrillary tangles in neurons, suggesting potential interaction between tau and TDP-43 pathologies.

TARGET GENE
MODEL SYSTEM
human postmortem brain tissue
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
RNA processing and gene expression regulation
SOURCE
extracted_from_pmid_34930382
PRIMARY OUTCOME
prevalence and distribution of TDP-43 pathology

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.800 composite

📖 Wiki Pages

TARDBP/TDP-43 ProteinproteinTARDBP Protein (TDP-43)proteinTARDBP — TAR DNA Binding Protein 43geneTARDBP Mutations in Amyotrophic Lateral SclerosisdiseaseTDP-43 ProteinredirectTDP-43 ProteinproteinTDP-43 ProteinproteinTDP-43 ProteinredirectTDP-43 RNA Granule PathwaymechanismTDP-43 DNA Repair Mechanism in ALS and DementiamechanismTDP-43 Pathology Reversibility in ALSmechanismTDP-43 Proteinopathymechanismtdp-43-fus-rna-proteinopathy-comparisonmechanismTDP-43 Co-pathology in Corticobasal SyndromemechanismTDP-43 Pathology in Corticobasal Syndromemechanism

Protocol

neuropathological examination of AD brain tissue using immunohistochemistry for phosphorylated TDP-43

Expected Outcomes

characterization of TDP-43 pathology frequency and anatomical distribution in AD

Success Criteria

detection and quantification of TDP-43 inclusions in brain regions

Related Hypotheses (4)

Cryptic Exon Silencing Restoration0.462
Cross-Seeding Prevention Strategy0.451
Glycine-Rich Domain Competitive Inhibition0.429
RNA-Binding Competition Therapy for TDP-43 Cross-Seeding0.374

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