ArticleJournal of neuropathology and experimental neurology2018
Detergent Insoluble Proteins and Inclusion Body-Like Structures Immunoreactive for PRKDC/DNA-PK/DNA-PKcs, FTL, NNT, and AIFM1 in the Amygdala of Cognitively Impaired Elderly Persons.
Article in Journal of neuropathology and experimental neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
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- Locus coeruleus TDP-43 pathology in a community-based cohort: Clinical and pathological correlates.Journal of neuropathology and experimental neurology · 2026Article
- Assessing Co-Localization of ITM2B With Alzheimer's Disease and Limbic-Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Changes.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025Article
- A pathologic study of Perivascular pTDP-43 Lin bodies in LATE-NC.Acta neuropathologica communications · 2024Article
- 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
- A high-throughput single-cell RNA expression profiling method identifies human pericyte markers.Neuropathology and applied neurobiology · 2023Article
- Human amygdala involvement in Alzheimer's disease revealed by stereological and dia-PASEF analysis.Brain pathology (Zurich, Switzerland) · 2023Article
- Transcriptome-wide association study identifies novel candidate susceptibility genes for migraine.HGG advances · 2023Article
- Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus.Clinical medicine insights. Endocrinology and diabetes · 2023Article
- Apolipoprotein E Proteinopathy Is a Major Dementia-Associated Pathologic Biomarker in Individuals with or without the APOE Epsilon 4 Allele.The American journal of pathology · 2022Article
- Alpha adaptins show isoform-specific association with neurofibrillary tangles in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Article
- Machine Learning Based Multimodal Neuroimaging Genomics Dementia Score for Predicting Future Conversion to Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Article
- The plasma peptides of Alzheimer's disease.Clinical proteomics · 2021Article
- Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain.Neurobiology of aging · 2021Article
- Pulse-Chase Proteomics of the App Knockin Mouse Models of Alzheimer's Disease Reveals that Synaptic Dysfunction Originates in Presynaptic Terminals.Cell systems · 2021Article
- Limbic-predominant age-related TDP-43 encephalopathy differs from frontotemporal lobar degeneration.Brain : a journal of neurology · 2020Article
- Diverse proteins aggregate in mild cognitive impairment and Alzheimer's disease brain.Alzheimer's research & therapy · 2020Article
- Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity.eLife · 2019Article
- TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.Neurobiology of disease · 2019Article
- Aging Neurovascular Unit and Potential Role of DNA Damage and Repair in Combating Vascular and Neurodegenerative Disorders.Frontiers in neuroscience · 2019Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Misfolded protein in the amygdala is a neuropathologic feature of Alzheimer disease and many other neurodegenerative disorders. We examined extracts from human amygdala (snap-frozen at autopsy) to investigate whether novel and as yet uncharacterized misfolded proteins would be detectable. Polypeptides from the detergent-insoluble, urea-soluble protein fractions of amygdala were interrogated using liquid chromatography-electrospray ionization-tandem mass spectrometry. Among the detergent-insoluble proteins identified in amygdala of demented subjects but not controls were Tau, TDP-43, Aβ, α-synuclein, and ApoE. Additional detergent-insoluble proteins from demented subjects in the high-molecular weight portion of SDS gels included NNT, TNIK, PRKDC (DNA-PK, or DNA-PKcs), ferritin light chain (FTL), AIFM1, SYT11, STX1B, EAA1, COL25A1, M4K4, CLH1, SQSTM, SYNJ1, C3, and C4. In follow-up immunohistochemical experiments, NNT, TNIK, PRKDC, AIFM1, and FTL were observed in inclusion body-like structures in cognitively impaired subjects' amygdalae. Double-label immunofluorescence revealed that FTL and phospho-PRKDC immunoreactivity colocalized partially with TDP-43 and/or Tau inclusion bodies. Western blots showed high-molecular weight "smears", particularly for NNT and PRKDC. A preliminary genetic association study indicated that rare NNT, TNIK, and PRKDC gene variants had nominally significant association with Alzheimer-type dementia risk. In summary, novel detergent-insoluble proteins, with evidence of proteinaceous deposits, were found in amygdalae of elderly, cognitively impaired subjects.
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