A5017339759- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Inflammation biomarkers and pathways
- Amyotrophic Lateral Sclerosis Research
Ludwig-Maximilians-Universität München
2023
University of Gothenburg
2023
German Center for Neurodegenerative Diseases
2022-2023
Abstract Loss-of-function variants of TREM2 are associated with increased risk Alzheimer’s disease (AD), suggesting that activation this innate immune receptor may be a useful therapeutic strategy. Here we describe high-affinity human TREM2-activating antibody engineered monovalent transferrin (TfR) binding site, termed transport vehicle (ATV), to facilitate blood–brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced...
Haploinsufficiency of the progranulin (PGRN)‐encoding gene (GRN) causes frontotemporal lobar degeneration (GRN‐FTLD) and results in microglial hyperactivation, TREM2 activation, lysosomal dysfunction, TDP‐43 deposition. To understand contribution hyperactivation to pathology, we used genetic pharmacological approaches suppress TREM2‐dependent transition microglia from a homeostatic disease‐associated state. Trem2 deficiency Grn KO mice reduced hyperactivation. explore antibody‐mediated...
With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.Using mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), genetically modified yield most opposite homeostatic (TREM2-knockout) disease-associated (GRN-knockout) states, we identified activity-dependent markers. Non-targeted mass spectrometry was used identify proteomic changes in cerebrospinal fluid (CSF) Grn-...
With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.Using mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), which were genetically modified yield most opposite homeostatic ( TREM2- knockout) disease-associated GRN -knockout) states, we identified activity-dependent markers. Non-targeted mass spectrometry was used identify changes in cerebrospinal (CSF) proteome Grn - Trem2...