ArticleJournal of neural transmission (Vienna, Austria : 1996)2016
Progranulin as a candidate biomarker for therapeutic trial in patients with ALS and FTLD.
Article in Journal of neural transmission (Vienna, Austria : 1996), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Pooled it
- A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.Alzheimer's research & therapy · 2024Pooled it
- Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review.Diagnostic pathology · 2024Pooled it
- Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Translational neurodegeneration · 2021Pooled it
- Blood-Based Biomarkers in Frontotemporal Dementia: A Narrative Review.International journal of molecular sciences · 2024Review
- Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials.Frontiers in aging neuroscience · 2024Article
- Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.Brain communications · 2023Review
- Blood Biomarkers in Frontotemporal Dementia: Review and Meta-Analysis.Brain sciences · 2021Review
- Frontotemporal dementia spectrum: first genetic screen in a Greek cohort.Neurobiology of aging · 2019Article
- CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline.EMBO molecular medicine · 2018Article
- Diagnostic value of cerebrospinal fluid tau, neurofilament, and progranulin in definite frontotemporal lobar degeneration.Alzheimer's research & therapy · 2018Article
- Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CSF Biomarkers of Neurodegeneration in Progressive Non-fluent Aphasia and Other Forms of Frontotemporal Dementia: Clues for Pathomechanisms?Frontiers in neurology · 2018Article
- CSF-Progranulin and Neurofilament Light Chain Levels in Patients With Radiologically Isolated Syndrome-Sign of Inflammation.Frontiers in neurology · 2018Article
- An 8-week, open-label, dose-finding study of nimodipine for the treatment of progranulin insufficiency fromAlzheimer's & dementia (New York, N. Y.) · 2017Article
- Imaging and fluid biomarkers in frontotemporal dementia.Nature reviews. Neurology · 2017Review
- Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers.Dementia and geriatric cognitive disorders extraArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The loss-of-function mechanism in progranulin (PGRN) mutation carriers makes PGRN an interesting target for upregulation as a therapeutic approach in neurodegenerative diseases like frontotemporal lobar degeneration. This gives rise to several questions: (1) how stable are PGRN levels in blood and cerebrospinal fluid (CSF) in follow-up? (2) Is it necessary to measure PGRN levels in CSF to monitor a therapeutic effect? Therefore, concentrations of PGRN were measured in paired CSF and serum samples of 22 patients with behavioural variant frontotemporal dementia, including one GRN mutation carrier (c.349+1G>C), 16 patients with amyotrophic lateral sclerosis and 17 non-neurodegenerative patients, which included 22 follow-up levels. PGRN levels of 14 patients with isolated dysfunction of the blood-CSF barrier were measured and PGRN was correlated with albumin quotients as a marker for blood-CSF barrier function. The intrathecal fraction of PGRN was calculated on the basis of CSF-to-serum ratios and hydrodynamic properties. Follow-up measurements of CSF and serum PGRN levels did not show any significant change in diagnostic groups. Mean PGRN levels are 35 times higher in blood than in CSF. However, the CSF-to-serum PGRN ratio does not correlate with the albumin quotient even in patients with severe impairment of the blood-CSF barrier. The calculated intrathecal fraction of CSF PGRN levels ranged between 80 and 90 %. Assuming that CSF PGRN is either brain-derived or transported from the vascular compartment via receptor mediated mechanisms, we propose that monitoring CNS specific effects of PGRN modulating drugs should be done in CSF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.