Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-Hakola disease, is a presenile dementia associated with loss of myelin, basal ganglia calcification, and bone cysts. It is caused by recessively inherited mutations in two genes encoding subunits of a cell membrane-associated receptor complex: TREM2 and DAP12. The clinical course of PLOSL has not been characterized in a series of patients with TREM2 mutations. The authors compare neurologic and neuroradiologic follow-up data of six patients carrying TREM2 mutations with PLOSL due to defective DAP12 genes. The authors review the known mutations in these two genes. Mutations in DAP12 and TREM2 result in a uniform disease phenotype. In Finnish and Japanese patients with PLOSL, DAP12 mutations predominate, whereas TREM2 is mutated more frequently elsewhere. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy should be considered in adult patients under age 50 years with dementia and basal ganglia calcification. Radiographs of ankles and wrists, and DNA test in uncertain cases, confirm the diagnosis.
Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS disorders with abnormalities in pathways of actin bundling and immune response
Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease
Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease
Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids
Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation
OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice
The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia
Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease
Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement
Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): a new report of an Italian woman and review of the literature
Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status
A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate
Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration
Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population
R47H TREM2 variant increases risk of typical early-onset Alzheimer's disease but not of prion or frontotemporal dementia
TREM2 Protein Expression Changes Correlate with Alzheimer's Disease Neurodegenerative Pathologies in Post-Mortem Temporal Cortices
Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice
Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease
Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia
What happens to microglial TREM2 in Alzheimer's disease: Immunoregulatory turned into immunopathogenic?
Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population
Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family
Production of wild-type and mutant-type human DAP12 proteins by Bombyx mori nucleopolyhedrovirus vector
Association study of TREM2 polymorphism rs75932628 with leucoaraiosis or Parkinson's disease in the Han Chinese population
Diagnostic Value of Brain Calcifications in Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.
TREM2 variants in neurodegenerative disorders in the Polish population. Homozygosity and compound heterozygosity in FTD patients
Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment
Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study
Behavioral Variant Frontotemporal Dementia-like Syndrome With Novel Heterozygous TREM2 Frameshift Mutation
The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism
An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function
TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant
Role of TREM2 in Alzheimer's Disease and its Consequences on β- Amyloid, Tau and Neurofibrillary Tangles
CLEC4C p.K210del variant causes impaired cell surface transport in plasmacytoid dendritic cells of amyotrophic lateral sclerosis
Different mechanisms of apolipoprotein E isoform-dependent modulation of prostaglandin E2 production and triggering receptor expressed on myeloid cells 2 (TREM2) expression after innate immune activation of microglia
Activation of FAK/Rac1/Cdc42-GTPase signaling ameliorates impaired microglial migration response to Aβ42 in triggering receptor expressed on myeloid cells 2 loss-of-function murine models.
TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy
Therapeutic Trem2 activation ameliorates amyloid-beta deposition and improves cognition in the 5XFAD model of amyloid deposition
The Emerging Role of Triggering Receptor Expressed on Myeloid Cells 2 as a Target for Immunomodulation in Ischemic Stroke
Neurodegenerative Disease-Associated Variants in TREM2 Destabilize the Apical Ligand-Binding Region of the Immunoglobulin Domain
Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis.
Phenotypic Expansion in Nasu-Hakola Disease: Immunological Findings in Three Patients and Proposal of a Unifying Pathogenic Hypothesis
Ocular hypertension suppresses homeostatic gene expression in optic nerve head microglia of DBA/2 J mice.
Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains
Expression of GPR17, a regulator of oligodendrocyte differentiation and maturation, in Nasu-Hakola disease brains
Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease
The Triggering Receptor Expressed on Myeloid Cells 2: A Molecular Link of Neuroinflammation and Neurodegenerative Diseases.
Reactive astrocytes express Aggregatin (FAM222A ) in the brains of Alzheimer's disease and Nasu-Hakola disease
Caldecrin inhibits lipopolysaccharide-induced pro-inflammatory cytokines and M1 macrophage polarization through the immunoreceptor triggering receptor expressed in myeloid cells-2
The Role of Microglia in Inherited White-Matter Disorders and Connections to Frontotemporal Dementia.
Alzheimer's Disease: Genetics
Alzheimer's disease is a neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations with this feed.
Basal Ganglia Cerebrovascular Disease
Basal ganglia cerebrovascular disease is a condition where the blood vessels in the basal ganglia are damaged or malfunction. Discover the latest research on basal ganglia cerebrovascular disease here.