ArticleActa neuropathologica2010
Brain progranulin expression in GRN-associated frontotemporal lobar degeneration.
Article in Acta neuropathologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
- Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration.Archives of neurology · 2011Trial
- Targeting Granulin Haploinsufficiency in Frontotemporal Dementia: From Genetic Mechanisms to Therapeutics.International journal of molecular sciences · 2025Review
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia.Journal of neuroinflammation · 2024Article
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations.Acta neuropathologica communications · 2023Article
- Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations.Brain : a journal of neurology · 2022Article
- Regulation of lysosomal trafficking of progranulin by sortilin and prosaposin.Brain communications · 2022Article
- Microglia regulate brain progranulin levels through the endocytosis/lysosomal pathway.JCI insight · 2021Article
- Article
- Neuropathological and behavioral characterization of aged Grn R493X progranulin-deficient frontotemporal dementia knockin mice.Acta neuropathologica communications · 2021Article
- Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration.Journal of neuroinflammation · 2020Article
- Approaches to develop therapeutics to treat frontotemporal dementia.Neuropharmacology · 2020Review
- FTLD-TDP With and Without GRN Mutations Cause Different Patterns of CA1 Pathology.Journal of neuropathology and experimental neurology · 2019Article
- Microglial Progranulin: Involvement in Alzheimer's Disease and Neurodegenerative Diseases.Cells · 2019Review
- AAV-Mediated Progranulin Delivery to a Mouse Model of Progranulin Deficiency Causes T Cell-Mediated Toxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Inflammasome signalling in brain function and neurodegenerative disease.Nature reviews. Neuroscience · 2018Review
- Selective depletion of microglial progranulin in mice is not sufficient to cause neuronal ceroid lipofuscinosis or neuroinflammation.Journal of neuroinflammation · 2017Article
- Disease and Region Specificity of Granulin Immunopositivities in Alzheimer Disease and Frontotemporal Lobar Degeneration.Journal of neuropathology and experimental neurology · 2017Article
- Restoring neuronal progranulin reverses deficits in a mouse model of frontotemporal dementia.Brain : a journal of neurology · 2017Article
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10 authors at 1 institution in 1 country.
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Abstract
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is characterized by progressive decline in behavior, executive function, and language. Progranulin (GRN) gene mutations are pathogenic for FTLD-TDP, and GRN transcript haploinsufficiency is the proposed disease mechanism. However, the evidence for this hypothesis comes mainly from blood-derived cells; we measured progranulin expression in brain. We characterized mRNA and protein levels of progranulin from four brain regions (frontal cortex, temporal cortex, occipital cortex, and cerebellum) in FTLD-TDP patients with and without GRN mutations, as well as neurologically normal individuals. Moreover, we performed immunohistochemistry to evaluate the degree of TDP-43 pathology and microglial infiltration present in these groups. In most brain regions, patients with GRN mutations showed mRNA levels comparable to normal controls and to FTLD-TDP without GRN mutations. However, GRN transcript levels in a brain region severely affected by disease (frontal cortex) were increased in mutation-bearing patients. When compared with normal individuals, GRN mutation-bearing cases had a significant reduction in the amount of progranulin protein in the cerebellum and occipital cortex, but not in the frontal and temporal cortices. In GRN mutant cases, GRN mRNA originated from the normal allele, and moderate microglial infiltration was observed. In conclusion, GRN mutation carriers have increased levels of mRNA transcript from the normal allele in brain, and proliferation of microglia likely increases progranulin levels in affected regions of the FTLD-TDP brain, and whether or not these findings underlie the accumulation of TDP-43 pathology in FTLD-TDP linked to GRN mutations remains to be determined.
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