ArticleNeurogenetics2015
Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease.
Article in Neurogenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 37 citations in OpenAlex.
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- TREM2 activation by first-in-class direct small molecule agonists: DEL screening, optimization, biophysical validation, and functional characterization.European journal of medicinal chemistry · 2026Article
- TREM2 and microglial immunity in Alzheimer's disease: mechanisms, genetics, and therapeutic opportunities.Frontiers in immunology · 2026Review
- DAP12 deletion reduces neuronal SLIT2 and demyelination and enhances brain resilience in female tauopathy mice.Molecular neurodegeneration · 2025Article
- Review
- Homozygous TREM2 c.549del; p.(Leu184Serfs*5) variant causing Nasu-Hakola disease in three siblings in a consanguineous Iraqi family: Case report and review of literature.Molecular genetics & genomic medicine · 2024Review
- Decoding sTREM2: its impact on Alzheimer's disease - a comprehensive review of mechanisms and implications.Frontiers in aging neuroscience · 2024Review
- Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia.Nature immunology · 2023Article
- The Primary Microglial Leukodystrophies: A Review.International journal of molecular sciences · 2022Review
- Alcohol, inflammation, and blood-brain barrier function in health and disease across development.International review of neurobiology · 2022Review
- TREM2 ectodomain and its soluble form in Alzheimer's disease.Journal of neuroinflammation · 2020Review
- Reduction of the RNA Binding Protein TIA1 Exacerbates Neuroinflammation in Tauopathy.Frontiers in neuroscience · 2020Article
- Could Alzheimer's Disease Originate in the Periphery and If So How So?Molecular neurobiology · 2019Review
- Potential Immunotherapeutic Targets on Myeloid Cells for Neurovascular Repair After Ischemic Stroke.Frontiers in neuroscience · 2019Review
- The Role of APOE and TREM2 in Alzheimer's Disease-Current Understanding and Perspectives.International journal of molecular sciences · 2018Review
- Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis.Cell reports · 2018Article
- Nasu Hakola Disease: A Rare Cause of Dementia and Cystic Bone Lesions, Report of a New Turkish Family.Noro psikiyatri arsivi · 2018Article
- Erythromyeloid-Derived TREM2: A Major Determinant of Alzheimer's Disease Pathology in Down Syndrome.Journal of Alzheimer's disease : JAD · 2018Article
- Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.Brain pathology (Zurich, Switzerland) · 2017Article
- TREM2 in Neurodegenerative Diseases.Molecular neurodegeneration · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nasu-Hakola disease (NHD) is a form of presenile dementia associated with sclerosing leukoencephalopathy and polycystic lipomembranous osteodysplasia. This extremely rare inherited disease is caused by mutations in either DAP12 or TREM2. The present study was designed to assess the relationship between DAP12/TREM2 genotype, mRNA and protein expression levels by both Western blotting and immunohistochemistry, and the tissue distribution and pathomorphological phenotype of the microglia. Molecular genetic testing performed in three NHD cases confirmed that two cases had mutations in DAP12 and that one case carried a mutation in TREM2. Protein levels were analyzed in four cases. Interestingly, significant DAP12 expression was found in numerous microglia in one NHD case with a homozygous DAP12 single-base substitution, and both real-time PCR and Western blotting confirmed the finding. In contrast, levels of both DAP12 and TREM2, respectively, were much lower in the other cases. Immunohistochemistry using established microglial markers revealed consistently mild activation of microglia in the cerebral white matter although there was no or only little expression of DAP12 in three of the NHD cases. The highly different expression of DAP12 represents the first description of such variable expressivity in NHD microglia. It raises important questions regarding the mechanisms underlying dementia and white matter damage in NHD.
Indexed as
Identifiers
What OpenQuestion holds
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.