Data files

The beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we performed glycoprotein enrichment and subsequent discovery proteomics to identify substrates of the protease BACE2 in plasma of mice. Therefore, we analysed plasma from BACE2 KO, BACE1/2 double KO and WT controls, as well as BACE1 KO with a separate ...

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. Here we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient loss of dendritic spines. Spines destined ...

We developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of T helper cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system in a model for Multiple Sclerosis are distinct.

We developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of T helper cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system in a model for Multiple Sclerosis are distinct.

Single-cell transcriptome profiling of disease-related lymphocytes in patients with multiple sclerosis

Here, we use in vivo labeling at defined anatomical sites for "provance" tracking of immune cells across compartmental borders in the context of experimental autoimmune encephalomyelitis (EAE). Specifically, we labeled T cells in mesenteric or inguinal lymph nodes (LNs) of T cell conditional mitoDendra2 reporter mice via photoconversion at disease onset and re-isolated photoconverted T cells form the LNs, spleen and CNS two days later and we performed scRNA-seq on them. Our experimental system ...

Here we investigated the earliest possible evidence of subclinical neuro-inflammation (SCNI) using a small cohort of monozygotic twins where one sibling had clinically definite MS and the other been clinically "healthy" but has a maximal genetic for developing MS. In contrast to subjects with radiologically isolated syndrome (RIS), our group of very early SCNI does not even fulfill the (arbitrary) MRI criteria for RIS but have more subtle MRI changes and/or evidence of neuro-inflammation in the ...