Data files

Here, we took advantage of well-defined mouse models for α-synucleinopathy (A30P-αS ) to explore proteome changes in the cerebrospinal fluid which are related to these distinct proteopathic lesions. Non-targeted liquid chromatography-mass spectrometry revealed that the majority of proteins that undergo age- and disease-related changes in either mouse model was linked to microglia, and more specifically to previously described disease state-specific microglia transcriptomic signatures. The finding ...

Here, we took advantage of well-defined mouse models for β-amyloidosis (APPPS1) to explore proteome changes in the cerebrospinal fluid which are related to these distinct proteopathic lesions. Non-targeted liquid chromatography-mass spectrometry revealed that the majority of proteins that undergo age- and disease-related changes in either mouse model was linked to microglia, and more specifically to previously described disease state-specific microglia transcriptomic signatures. The finding that ...

The earliest defining event in the pathogenesis of Alzheimer´s disease (AD) is the intracerebral deposition of Abeta, which starts at least 20 years before the onset of dementia. The link between Abeta and downstream neurodegeneration leading to dementia remains unclear, a critical gap in knowledge at a time when clinical trials are increasingly shifting to pre-symptomatic disease stages. Consequently, the design of preventive treatment strategies based on biomarkers remains an important challenge. ...

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of biological specimens imaged in 3D as a whole are lacking. Here, we present DISCO-MS, a technology combining whole-organ/ism imaging, deep learning-based image analysis, robotic tissue extraction and ultra-high sensitivity mass spectrometry. DISCO-MS yielded qualitative and quantitative proteomics data indistinguishable ...

Amyloid-beta (Aβ) deposition is an initiating factor in Alzheimer´s disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating phagocytic function. Immunotherapies are currently pursued as therapeutic strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. Here, we evaluated ...

Hereditary sensory and autonomic neuropathy 9 (HSAN9) is a rare neurological disease caused by mutations in the gene encoding for Tectonin β-propeller repeat containing protein 2 (TECPR2) which possibly result in loss of the protein. Beside its potential role in autophagy, TECPR2 may serve as positive modulator of COPII-mediated ER export. However, the molecular consequences of TECPR2 deficiency for the secretory pathway remain unclear, in particular with regard to specific cargo proteins. By ...

The protease BACE1 is a major drug target for Alzheimer’s disease, but chronic BACE1 inhibition is associated with non-progressive worsening that may be caused by modulation of unknown physiological BACE1 substrates. To identify in vivo-relevant BACE1 substrates we applied pharmacoproteomics to non-human-primate cerebrospinal fluid (CSF) after acute treatment with BACE inhibitors. Besides SEZ6, the strongest, dose-dependent reduction was observed for the pro-inflammatory cytokine receptor ...