ArticleJournal of Alzheimer's disease : JAD2023
Comparison of Clinical, Genetic, and Pathologic Features of Limbic and Diffuse Transactive Response DNA-Binding Protein 43 Pathology in Alzheimer's Disease Neuropathologic Spectrum.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Clinical, Radiological, and Immunohistological Distinctions Between Limbic-Predominant and Typical Alzheimer's Disease: A Systematic Review.Brain and behavior · 2026Pooled it
- 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
- FDG-PET imaging to identify brain regions associated with Alzheimer's disease-related TDP-43 proteinopathy: A predictive model using penalized logistic regression analysis.Journal of Alzheimer's disease : JAD · 2026Article
- 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
- LATE-NC Stage 3: a diagnostic rubric to differentiate severe LATE-NC from FTLD-TDP.Acta neuropathologica · 2025Article
- Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis.Journal of neuropathology and experimental neurology · 2024Review
- Senile plaque-associated transactive response DNA-binding protein 43 in Alzheimer's disease: A case report spanning 16 years of memory loss.Neuropathology : official journal of the Japanese Society of Neuropathology · 2024Article
- Clinicopathologic features of a novel star-shaped transactive response DNA-binding protein 43 (TDP-43) pathology in the oldest old.Journal of neuropathology and experimental neurology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundIncreasing evidence suggests that TAR DNA-binding protein 43 (TDP-43) pathology in Alzheimer's disease (AD), or AD-TDP, can be diffuse or limbic-predominant. Understanding whether diffuse AD-TDP has genetic, clinical, and pathological features that differ from limbic AD-TDP could have clinical and research implications.
objectiveTo better characterize the clinical and pathologic features of diffuse AD-TDP and differentiate it from limbic AD-TDP.
methods363 participants from the Mayo Clinic Study of Aging, Alzheimer's Disease Research Center, and Neurodegenerative Research Group with autopsy confirmed AD and TDP-43 pathology were included. All underwent genetic, clinical, neuropsychologic, and neuropathologic evaluations. AD-TDP pathology distribution was assessed using the Josephs 6-stage scale. Stages 1-3 were classified as Limbic, those 4-6 as Diffuse. Multivariable logistic regression was used to identify clinicopathologic features that independently predicted diffuse pathology.
resultsThe cohort was 61% female and old at onset (median: 76 years [IQR:70-82]) and death (median: 88 years [IQR:82-92]). Fifty-four percent were Limbic and 46% Diffuse. Clinically, ∼10-20% increases in odds of being Diffuse associated with 5-year increments in age at onset (p = 0.04), 1-year longer disease duration (p = 0.02), and higher Neuropsychiatric Inventory scores (p = 0.03), while 15-second longer Trailmaking Test-B times (p = 0.02) and higher Block Design Test scores (p = 0.02) independently decreased the odds by ~ 10-15%. There was evidence for association of APOEɛ4 allele with limbic AD-TDP and of TMEM106B rs3173615 C allele with diffuse AD-TDP. Pathologically, widespread amyloid-β plaques (Thal phases: 3-5) decreased the odds of diffuse TDP-43 pathology by 80-90%, while hippocampal sclerosis increased it sixfold (p < 0.001).
conclusionDiffuse AD-TDP shows clinicopathologic and genetic features different from limbic AD-TDP.
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