ArticleAnnals of clinical and translational neurology2019
Microglia in frontotemporal lobar degeneration with progranulin or C9ORF72 mutations.
Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Microglial progranulin differently regulates hypothalamic lysosomal function in lean and obese conditions via cleavage-dependent mechanisms.Journal of neuroinflammation · 2025Article
- Selective cellular and regional vulnerability in frontotemporal lobar degeneration: a scoping review.Free neuropathology · 2025Review
- Imaging of the superficial white matter in health and disease.Imaging neuroscience (Cambridge, Mass.) · 2024Article
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia.Brain : a journal of neurology · 2023Article
- Cortical iron accumulation in MAPT- and C9orf 72-associated frontotemporal lobar degeneration.Brain pathology (Zurich, Switzerland) · 2023Article
- White-matter abnormalities in presymptomaticBrain communications · 2023Article
- Inflammation context in Alzheimer's disease, a relationship intricate to define.Biological research · 2022Review
- The role of inflammation in neurodegeneration: novel insights into the role of the immune system in C9orf72 HRE-mediated ALS/FTD.Molecular neurodegeneration · 2022Review
- Cellular and pathological heterogeneity of primary tauopathies.Molecular neurodegeneration · 2021Review
- Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated WithFrontiers in aging neuroscience · 2021Article
- Glycoprotein Pathways Altered in Frontotemporal Dementia With Autoimmune Disease.Frontiers in immunology · 2021Article
- An update on the rod microglia variant in experimental and clinical brain injury and disease.Brain communications · 2021Review
- Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration.Journal of neuroinflammation · 2020Article
- White matter hyperintensities in progranulin-associated frontotemporal dementia: A longitudinal GENFI study.NeuroImage. Clinical · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveTo identify clinicopathological differences between frontotemporal lobar degeneration (FTLD) due to mutations in progranulin (FTLD-GRN) and chromosome 9 open reading frame 72 (FTLD-C9ORF72).
methodsWe performed quantitative neuropathologic comparison of 17 FTLD-C9ORF72 and 15 FTLD-GRN with a focus on microglia. For clinical comparisons, only cases with high quality medical documentation and concurring diagnoses by at least two neurologists were included (14 FTLD-GRN and 13 FTLD-C9ORF72). Neuropathological analyses were limited to TDP-43 Type A to assure consistent assessment between the groups, acknowledging that Type A is a minority of C9ORF72 patients. Furthermore, only cases with sufficient tissue from all regions were studied (11 FTLD-GRN and 11 FTLD-C9ORF72). FTLD cases were also compared to age- and sex-matched normal controls. Immunohistochemistry was performed for pTDP-43, IBA-1, CD68, and GFAP. Morphological characterization of microglia was performed in sections of cortex blinded to clinical and genetic information.
resultsFTLD-GRN patients had frequent asymmetric clinical features, including aphasia and apraxia, as well as more asymmetric cortical atrophy. Neuropathologically, FTLD-C9ORF72 had greater hippocampal tau pathology and more TDP-43 neuronal cytoplasmic inclusions. FTLD-GRN had more neocortical microvacuolation, as well as more IBA-1-positive ameboid microglia in superficial cortical layers and in subcortical white matter. FTLD-GRN also had more microglia with nuclear condensation, possibly indicating apoptosis. Microglial morphology with CD68 immunohistochemistry in FTLD-GRN and FTLD-C9ORF72 differed from controls.
interpretationOur findings underscore differences in microglial response in FTLD-C9ORF72 and FTLD-GRN as shown by significant differences in ameboid microglia in gray and white matter. These results suggest the differential contribution of microglial dysfunction in FTLD-GRN and FTLD-C9ORF72 and suggest that clinical, neuroimaging and pathologic differences could in part be related to differences in microglia response.
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