Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment on transplant connectivity. To explore the effect of amyloid pathology in Alzheimer's disease (AD) and aging, we examined graft connectivity using monosynaptic rabies virus tracing in APP/PS1 mice and in 16- to 18-month-old wild-type (WT) mice. Transplanted neurons differentiated within 4 weeks and integrated well into the host visual cortex, receiving input from the appropriate brain regions for this area. Unexpectedly, we found a prominent several-fold increase in local inputs, in both amyloid-loaded and aged environments. State-of-the-art deep proteome analysis using mass spectrometry highlights complement system activation as a common denominator of environments promoting excessive local input connectivity. These data therefore reveal the key role of the host pathology in shaping the input connectome, calling for caution in extrapolating results from one pathological condition to another.
Export PNG
Views: 83
Created: 15th Oct 2024 at 13:13
This item has not yet been tagged.
Related items
Projects: Published Datasets, Unpublished Datasets
Institutions: Helmholtz Munich, LMU
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Projects: Published Datasets, Unpublished Datasets
Institutions: LMU Klinikum
Research Data Manager
This project serves as a centralized repository for omics datasets published by research groups within the SyNergy Cluster. It encompasses investigations such as proteomics and transcriptomics, which are further divided into individual studies led by SyNergy members. Each study is linked to relevant publications, assays and data files (with links to external repositories).
To explore investigations and their associated studies in more detail, please visit the 'Related items' tab on the Project ...
Public web page: Not specified
Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa, Danio rerio
Submitter: Rainer Malik
Studies: A TBK1 variant causes autophagolysosomal and motoneuron pathology withou..., A ubiquitin-specific, proximity-based labeling approach for the identifi..., ACSL3 is a novel GABARAPL2 interactor that links ufmylation and lipid dr..., ADAM10-Mediated Ectodomain Shedding Is an Essential Driver of Podocyte D..., ALS-linked loss of Cyclin-F function affects HSP90, AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal..., ATG4 family proteins drive phagophore growth independently of the LC3/GA..., An optimized quantitative proteomics method establishes the cell type-re..., Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mit..., Autophagosome content profiling using proximity biotinylation proteomics..., Autophagy acts through TRAF3 and RELB to regulate gene expression via an..., Basic Fibroblast Growth Factor 2-Induced Proteome Changes Endorse Lewy B..., Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Micro..., Brain injury environment critically influences the connectivity of trans..., C9orf72 protein quality control by UBR5-mediated heterotypic ubiquitin c..., CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boos..., Cell-type-specific profiling of brain mitochondria reveals functional an..., Cellular depletion of major cathepsin proteases reveals their concerted ..., Deciphering sources of PET signals in the tumor microenvironment of glio..., Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regula..., Development of a Proteomic Workflow for the Identification of Heparan Su..., Distinct molecular profiles of skull bone marrow in health and neurologi..., Excessive local host-graft connectivity in aging and amyloid-loaded brain, Experimental evidence for temporal uncoupling of brain Aβ deposition and..., Fibrillar Aβ triggers microglial proteome alterations and dysfunction in..., Filling the Gaps – A Call for Comprehensive Analysis of Extracellular Ma..., IKKβ binds NLRP3 providing a shortcut to inflammasome activation for rap..., Injury-specific factors in the cerebrospinal fluid regulate astrocyte pl..., Lipid and protein content profiling of isolated native autophagic vesicles, Loss of CLN3 in microglia leads to impaired lipid metabolism and myelin ..., Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in..., Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH, Lysosomal targeting of the ABC transporter TAPL is determined by membran..., Mapping autophagosome contents identifies interleukin-7 receptor-alpha a..., Met/HGFR triggers detrimental reactive microglia in TBI, MicroRNAs from extracellular vesicles as a signature for Parkinson's dis..., Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD..., Multiomic ALS signatures highlight subclusters and sex differences sugge..., Neuronal differentiation of LUHMES cells induces substantial changes of ..., Nonvesicular lipid transfer drives myelin growth in the central nervous ..., NrCAM is a marker for substrate-selective activation of ADAM10 in Alzhei..., Pro-inflammatory activation following demyelination is required for myel..., Proteomic Characterization of Ubiquitin Carboxyl-Terminal Hydrolase 19 D..., Proteomic and lipidomic profiling of demyelinating lesions identifies fa..., Proteomic profiling in cerebral amyloid angiopathy reveals an overlap wi..., Proteomics of mouse brain endothelium uncovers dysregulation of vesicula..., Rational correction of pathogenic conformational defects in HTRA1, Reactivated endogenous retroviruses promote protein aggregate spreading, Signal peptide peptidase-like 2c impairs vesicular transport and cleaves..., Signatures of glial activity can be detected in the CSF proteome, Spatial centrosome proteome of human neural cells uncovers disease-relev..., Spatial proteomics in three-dimensional intact specimens, Spatial proteomics reveals secretory pathway disturbances caused by neur..., Systematically defining selective autophagy receptor-specific cargo usin..., Targeting the TCA cycle can ameliorate widespread axonal energy deficien..., The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 si..., The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulat..., The COP9 signalosome reduces neuroinflammation and attenuates ischemic n..., The Hippo network kinase STK38 contributes to protein homeostasis by inh..., The intramembrane protease SPPL2c promotes male germ cell development by..., The pseudoprotease iRhom1 controls ectodomain shedding of membrane prote..., The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor com..., The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in respon..., Trnp1 organizes diverse nuclear membrane-less compartments in neural ste..., Ubiquitin profiling of lysophagy identifies actin stabilizer CNN2 as a t...
Assays: Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Affinity purification coupled with mass spectrometry proteomics (human), Bottom-up proteomics (human), Bottom-up proteomics (mouse), Bottom-up proteomics (mouse), Bottom-up proteomics (mouse), Bottom-up proteomics (mouse), Gel-based experiment (human), Phosphoproteomics / Bottom-up proteomics (mouse), Proximity-proteomics-based autophagosome content profiling (human), SWATH MS (human), SWATH MS (human, mouse), SWATH MS (mouse), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human), Shotgun proteomics (human, mouse), Shotgun proteomics (human, mouse), Shotgun proteomics (human, mouse), Shotgun proteomics (human, mouse), Shotgun proteomics (macaque), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (mouse), Shotgun proteomics (rat), Untargeted Proteomics (mouse)
Snapshots: Snapshot 1
8 months old control C57BL/6J (n=10), 17 months aged C57BL/6J (n=4), and 8 months old APP/PS1 mice (n=5) were sacrificed through cervical dislocation, brains were removed and placed into cold 1x PBS. Biopsy punches of the visual cortex of both hemispheres were taken with a tissue puncher (2.5 mm diameter) and meninges and white matter were carefully removed using forceps to have a tissue sample consisting of grey matter only. Each sample was put into a low-protein binding Eppendorf tube, frozen ...
Submitter: Aditi Methi
Assay type: Proteomics
Technology type: Technology Type
Investigation: Proteomics (Published)
Organisms: Mus musculus
SOPs: No SOPs
Data files: Excessive local host-graft connectivity in aged...
Snapshots: No snapshots
Creators: None
Submitter: Aditi Methi
Investigations: Proteomics (Published)
Studies: Excessive local host-graft connectivity in agin...
Assays: Shotgun proteomics (mouse)
Abstract (Expand)
Authors: Judith Thomas, Maria Fernanda Martinez-Reza, Manja Thorwirth, Yvette Zarb, Karl-Klaus Conzelmann, Stefanie M Hauck, Sofia Grade, Magdalena Götz
Date Published: 10th Jun 2022
Publication Type: Journal