Publications by authors named "Estibaliz Lopez-Rodrigo"
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however, few studies have investigated its role in neurodegenerative processes such as Alzheimer's disease (AD). Here, we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations.
View Article and Find Full Text PDFLangerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders associated with mitogen-activated protein (MAP)-kinase-activating mutations and an increased risk of neurodegeneration. We found microglial mutant clones in LCH and ECD patients, whether or not they presented with clinical symptoms of neurodegeneration, associated with microgliosis, astrocytosis, and neuronal loss, predominantly in the rhombencephalon gray nuclei. Neurological symptoms were associated with PU.
View Article and Find Full Text PDFArticle Synopsis
- Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are linked to certain genetic mutations and pose a heightened risk for neurodegeneration, revealing microglia mutant clones in patients' brains.
- These mutant clones lead to symptoms like microgliosis and neuronal loss, notably affecting specific brain regions, with symptoms correlating to the disease's duration and the size of these clones.
- Research suggests that targeting these mutant microglia with a CSF1R-inhibitor could prevent neuronal loss, presenting a potential new treatment option distinct from current MAPK inhibitors.
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer's Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations.
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- Histiocytoses are blood disorders linked to mutations in certain kinases, particularly BRAF and MEK1/MEK2.
- The causes of histiocytosis in patients are still unclear, and alternative treatment options beyond BRAF and MEK remain undefined.
- This study found that mutations in CSF1R and changes in RET and ALK lead to significant responses to specific drugs, selpercatinib and crizotinib, in patients with histiocytosis.