ArticleActa neuropathologica2019
Pathological, imaging and genetic characteristics support the existence of distinct TDP-43 types in non-FTLD brains.
Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed, 106 citations in OpenAlex.
- TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The UNC13A cryptic exon associates with cognitive impairment in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Artificial intelligence-based 3D segmentation of tangle-associated TDP-43 in neurodegeneration.Brain pathology (Zurich, Switzerland) · 2026Article
- A phosphorylation‑independent monoclonal antibody improves detection of TDP‑43 pathology across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and limbic predominant age related TDP‑43 encephalopathy neuropathological change.Journal of neuropathology and experimental neurology · 2026Article
- Brain morphometry patterns in the presence of Alzheimer's disease and/or LATE neuropathologic changes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Biochemical and Immunohistochemical Associations of TDP-43 and Cryptic RNA With Hippocampal and Amygdala Volumetrics in Alzheimer's Disease.Annals of neurology · 2026Article
- Molecular signatures and biomarker development for limbic-predominant age-related TDP-43 encephalopathy (LATE).Acta neuropathologica · 2026Review
- Comparative effects of TDP-43-A and TDP-43-α on hippocampal subfields and amygdala nuclei.Journal of Alzheimer's disease : JAD · 2026Article
- Hippocampal subfield thickness and shape analysis in examining the impact of TDP-43 in primary age-related tauopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Differences and overlaps in TDP-43 pathology of 'pure' LATE-NC compared to LATE-NC coexisting with Alzheimer's disease.Acta neuropathologica · 2025Article
- Multiple Neuropathologies Underly Hippocampal Subfield Atrophy in a Case With a Slowly Progressive Amnestic Syndrome: Challenging the Notion of Pure LATE-NC.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Relation of Alzheimer's disease-related TDP-43 proteinopathy to metrics from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).Neurobiology of aging · 2025Article
- Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.Nature communications · 2025Article
- Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.Journal of neuropathology and experimental neurology · 2025Article
- Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia.NPJ dementia · 2025Article
- Evaluating the updated LATE-NC staging criteria using data from NACC.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer's disease continuum.Acta neuropathologica · 2024Article
- TDP-43 in nuclear condensates: where, how, and why.Biochemical Society transactions · 2024Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
TDP-43 is present in a high proportion of aged brains that do not meet criteria for frontotemporal lobar degeneration (FTLD). We determined whether there are distinct TDP-43 types in non-FTLD brains. From a cohort of 553 brains (Braak neurofibrillary tangle (NFT) stage 0-VI), excluding cases meeting criteria for FTLD, we identified those that had screened positive for TDP-43. We reviewed 14 different brain regions in these TDP-43 positive cases and classified them into those with "typical" TDP-43 immunoreactive inclusions (TDP type-α), and those in which TDP-43 immunoreactivity was adjacent to/associated with NFTs in the same neuron (TDP type-β). We compared pathological, genetic (APOE4, TMEM106B and GRN variants), neuroimaging and clinical data between types, as well as compared neuroimaging between types and a group of TDP-43 negative cases (n = 309). Two-hundred forty-one cases were classified as TDP type-α (n = 131, 54%) or TDP type-β (n = 110, 46%). Type-α cases were older than type-β at death (median 89 years vs. 87 years; p = 0.02). Hippocampal sclerosis was present in 78 (60%) type-α cases and 16 (15%) type-β cases (p < 0.001). Type-α cases showed a pattern of widespread TDP-43 deposition commonly extending into temporal, frontal and brainstem regions (84% TDP-43 stage 4-6) while in type-β cases deposition was predominantly limbic, located in amygdala, entorhinal cortex and subiculum of the hippocampus (84% TDP-43 stages 1-3) (p < 0.001). There was a difference in the frequency of TMEM106B protective (GG) and risk (CC) haplotypes (SNP rs3173615 encoding p.T185S) in type-α cases compared to type-β cases (GG/CG/CC: 8%/42%/50% vs. 24%/49%/27%; p = 0.01). Type-α cases had smaller amygdala (- 10.6% [- 17.6%, - 3.5%]; p = 0.003) and hippocampal (- 14.4% [- 21.6%, - 7.3%]; p < 0.001) volumes on MRI at death compared to type-β cases, although both types had smaller amygdala and hippocampal volumes compared to TDP-43 negative cases (- 7.77%, - 21.6%; p < 0.001). These findings demonstrate that there is distinct heterogeneity of TDP-43 deposition in non-FTLD brains.
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