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

TARDBP (Score: 0.514)

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

📖 Wiki Pages

TARDBP Protein (TDP-43)protein TARDBP Mutations in Amyotrophic Lateral Sclerosisdisease TARDBP/TDP-43 Proteinprotein TARDBP — TAR DNA Binding Protein 43gene TDP-43 Aggregate Neuronscell TDP-43 Proteinopathy Investment Landscapeinvestment TDP-43 Proteinopathy in Amyotrophic Lateral Scleromechanism TDP-43 Proteinopathy Neuronsredirect TDP-43 PET Ligand Development for FTD and ALSexperiment TDP-43 Pathology in Corticobasal Syndromedisease TDP-43 Proteinopathy Neurons in Frontotemporal Demcell TDP-43 PET Ligand Development for Frontotemporal Dgap TDP-43 (TAR DNA-Binding Protein 43) - Biomarkerbiomarker TDP-43 Splicing Modulation Therapyidea TDP-43 Proteinopathy Neuronscell

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 (8)

Cross-Seeding Prevention Strategy0.689

Glycine-Rich Domain Competitive Inhibition0.640

LRP1-Dependent Tau Uptake Disruption0.576

Cryptic Exon Silencing Restoration0.531

RNA-Binding Competition Therapy for TDP-43 Cross-Seeding0.465

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