A5070219552- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Cholinesterase and Neurodegenerative Diseases
- Machine Learning in Bioinformatics
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- Social and Educational Sciences
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Bioinformatics and Genomic Networks
- Monoclonal and Polyclonal Antibodies Research
- Health and Lifestyle Studies
- Biochemical and Structural Characterization
- African studies and sociopolitical issues
- Team Dynamics and Performance
- Glycosylation and Glycoproteins Research
- Insect Resistance and Genetics
- RNA Research and Splicing
- RNA regulation and disease
- Cell Adhesion Molecules Research
- Health and Well-being Studies
- Educational Tools and Methods
- Biomedical Ethics and Regulation
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
Aarhus University
2021-2024
Copenhagen Business School
2002
The established causal genes in Alzheimer's disease (AD), APP, PSEN1, and PSEN2, are functionally characterized using biomarkers, capturing an vivo profile reflecting the disease's initial preclinical phase. Mutations SORL1, encoding endosome recycling receptor SORLA, found 2%–3% of individuals with early-onset AD, SORL1 haploinsufficiency appears to be for AD. To test whether can function as AD gene, we use CRISPR-Cas9-based gene editing develop a model Göttingen minipigs, taking advantage...
SORL1 , the gene encoding large multidomain SORLA protein, has emerged as only fourth that when mutated can by itself cause Alzheimer’s disease (AD), and a reliably linked to both early- late-onset forms of disease. is known interact with endosomal trafficking regulatory complex called retromer in regulating recycling cargo, including amyloid precursor protein (APP) glutamate receptor GluA1. Nevertheless, SORLA’s precise structural–functional relationship tubules remains unknown. Here, we...
Abstract SorLA, encoded by the gene SORL1 , is an intracellular sorting receptor of VPS10P domain family. Although SorLA best recognized for its ability to shuttle target proteins between compartments in neurons, recent data suggest that also microglial expression can be high relevance pathogenesis brain diseases, including glioblastoma (GBM). Here, we interrogated impact on functional properties glioma-associated microglia and macrophages (GAMs). In GBM microenvironment, GAMs are...
Truncating genetic variants of SORL1 , encoding the endosome recycling receptor SORLA, have been accepted as causal Alzheimer’s disease (AD). However, most observed in are missense variants, for which it is complicated to determine pathogenicity level because carriers come from pedigrees too small be informative penetrance estimations. Here, we describe three unrelated families coding variant rs772677709, that leads a p.Y1816C substitution, segregates with disease. Further, investigate...
ABSTRACT SORL1 encodes the retromer-associated receptor SORLA that functions in endosomal recycling. Rare variants have been associated with Alzheimer’s disease (AD) and rare pathogenic are estimated to occur up 2.75% of early onset AD patients 1.5% unrelated late patients. While truncation mutations observed almost exclusively patients, it is currently unknown which among hundreds missense identified , pathogenic. Here we address this question by relying on SORLA’s distinct molecular...
Abstract SORL1 is strongly associated with both sporadic and familial forms of Alzheimer’s disease (AD), but a lack information about alternatively spliced transcripts currently limits our understanding the role in AD. Here, we describe transcript ( SORL1-38b ) characterized by inclusion novel exon (E38b) that encodes truncated protein. We identified E38b-containing several brain regions, highest expression cerebellum showed largely located neuronal dendrites, which contrast to somatic...
Abstract Background Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer’s disease (AD). SORL1 encodes retromer‐associated receptor SORLA plays an essential role AD‐associated cargos such as amyloid precursor protein and glutamatergic AMPA receptor. Importantly, loss function pathogenic variants are associated with AD. Moreover, both retromer levels reduced most vulnerable regions AD brains. Thus, restoration via viral...
ABSTRACT Truncating genetic variants of SORL1 , encoding the endosome recycling receptor SORLA, have been accepted as causal Alzheimer’s disease (AD). However, most observed in are missense variants, for which it is complicated to determine pathogenicity level because carriers come from pedigrees too small be informative penetrance estimations. Here, we describe three unrelated families coding variant rs772677709, that leads a p.Y1816C substitution, segregates with disease. Further,...
Abstract SorLA, encoded by the gene SORL1 , is an intracellular sorting receptor of VPS10P domain family. Although SorLA best recognized for its ability to shuttle target proteins between compartments in neurons, recent data suggest that also microglial expression can be high relevance pathogenesis brain diseases, including glioblastoma (GBM). Here we interrogated impact on functional properties glioma-associated microglia and macrophages (GAMs). In GBM microenvironment, GAMs are...
Reduced levels of the Sortilin-related receptor with A-type repeats (SORLA) in different brain regions as well cerebrospinal fluid have been associated Alzheimer's disease. Methods and reagents to develop reliable detection assays quantify SORLA its specific isoforms are therefore much needed. Nanobodies (Nbs) unique biomolecules derived from blood camelids that display advantageous physicochemical antigen affinity properties, making them attractive tools great relevance both diagnostic...
Abstract Background SORL1 encodes the retromer‐associated receptor SORLA that functions in endosomal recycling. Rare variants have been associated with Alzheimer’s disease (AD) and rare pathogenic are estimated to occur up 2.75% of early onset AD patients 1.5% unrelated late patients. While truncation mutations observed almost exclusively patients, it is currently unknown which among hundreds missense identified , pathogenic. Method Here we address this question by relying on SORLA’s...
ABSTRACT The few established causal genes in Alzheimer’s disease (AD), mutations APP and PSENs, have been functionally characterized using biomarkers, capturing an vivo profile reflecting the disease’s initial preclinical phase. SORL1 , a gene encoding endosome recycling receptor SORLA, epidemiologically behaves as when truncating lead to partial loss of protein function. Here, effort test whether can indeed function AD gene, we used CRISPR-Cas9-based editing develop novel model...
The few established causal genes in Alzheimer’s disease (AD), mutations APP and PSENs, have been functionally characterized using biomarkers, capturing an vivo profile reflecting the disease’s initial preclinical phase. SORL1, a gene encoding endosome recycling receptor SORLA, epidemiologically behaves as when truncating lead to partial loss of protein function. Here, effort test whether SORL1 can indeed function AD gene, we used CRISPR-Cas9-based editing develop novel model...