ArticleNeurobiology of disease2019
TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Data-driven thresholds for standardized classification of severe Alzheimer's disease neuropathology using digital neuropathology.Brain pathology (Zurich, Switzerland) · 2026Article
- ABCC9/SUR2 has a Complex Expression Pattern in Human Brain Gliovascular Unit Cells, Including Astrocytes.Journal of molecular neuroscience : MN · 2026Article
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Exploring the link between dystrophic microglia and the spread of Alzheimer's neuropathology.Brain : a journal of neurology · 2025Article
- Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.Acta neuropathologica communications · 2024Review
- A high-throughput single-cell RNA expression profiling method identifies human pericyte markers.Neuropathology and applied neurobiology · 2023Article
- In severe ADNC, hippocampi with comorbid LATE-NC and hippocampal sclerosis have substantially more astrocytosis than those with LATE-NC or hippocampal sclerosis alone.Journal of neuropathology and experimental neurology · 2023Article
- Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- When Alzheimer's is LATE: Why Does it Matter?Annals of neurology · 2023Review
- Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort.Acta neuropathologica communications · 2023Article
- Urinary Incontinence in a Community-Based Autopsy Cohort Is Associated with Limbic Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Changes.Journal of Alzheimer's disease : JAD · 2023Article
- Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts.Acta neuropathologica · 2022Article
- The Role of TDP-43 in Neurodegenerative Disease.Molecular neurobiology · 2022Review
- Patterns of amygdala region pathology in LATE-NC: subtypes that differ with regard to TDP-43 histopathology, genetic risk factors, and comorbid pathologies.Acta neuropathologica · 2022Article
- Limbic-Predominant Age-Related TDP-43 Encephalopathy: Medical and Pathologic Factors Associated With Comorbid Hippocampal Sclerosis.Neurology · 2022Article
- Alpha adaptins show isoform-specific association with neurofibrillary tangles in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Article
- Glial TDP-43 and TDP-43 induced glial pathology, focus on neurodegenerative proteinopathy syndromes.Glia · 2022Review
- Analysis of genes (TMEM106B, GRN, ABCC9, KCNMB2, and APOE) implicated in risk for LATE-NC and hippocampal sclerosis provides pathogenetic insights: a retrospective genetic association study.Acta neuropathologica communications · 2021Article
- Modulating Thyroid Hormone Levels in Adult Mice: Impact on Behavior and Compensatory Brain Changes.Journal of thyroid research · 2021Article
- Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Sensitivity, Specificity and Potential for Clinical Use.Journal of personalized medicine · 2020Review
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9 authors at 1 institution in 1 country.
Funding
Abstract
TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology in the hippocampal formation. Overall, 46.4% of the cases were positive for TDP-43 intracellular inclusions, which is consistent with results in other prior community-based cohorts. The pathologies were correlated with hippocampal sclerosis of aging (HS-Aging) linked genotypes. We also assayed brain parenchymal thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels. In cases with SLCO1A2/IAPP or ABCC9 risk associated genotypes, the T3/T4 ratio tended to be reduced (p = .051 using 2-tailed statistical test), and in cases with low T3/T4 ratios (bottom quintile), there was a higher likelihood of HS-Aging pathology (p = .025 using 2-tailed statistical test). This is intriguing because the SLCO1A2/IAPP and ABCC9 risk associated genotypes have been associated with altered expression of the astrocytic thyroid hormone receptor (protein product of the nearby gene SLCO1C1). These data indicate that dysregulation of thyroid hormone signaling may play a role in age-related TDP-43 proteinopathy.
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