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PXD050060 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBrain Creatine Kinase as a biomarker for Alzheimer’s disease
DescriptionThe creatine-phosphocreatine cycle serves as a crucial temporary energy buffering system in the brain, regulated by brain creatine kinase (CKB). CKB, responsible for reversible phosphorylation of creatine, plays a pivotal role in maintaining ATP levels. Alzheimer's disease (AD) has been linked to increased CKB oxidation and loss of its functions, although specific pathological processes and affected cell types remain unclear. In our study, cerebral cortex samples from AD, dementia with Lewy bodies (DLB), and age-matched controls were analyzed using antibody-based methods to quantify CKB levels and assess alterations associated with disease processes. Two independently validated antibodies exclusively labeled astrocytes in the human cerebral cortex. Immunofluorescence and Western blot analyses demonstrated a loss of CKB immunoreactivity correlated with increased plaque load, severity of tau pathology, and Lewy body pathology. Combining antibody-based and mass spectrometry (MS) approaches, we explored CKB availability in AD and DLB. Transcriptomics and targeted MS revealed unaltered total CKB levels. Reduced antibody binding levels, confirmed by Western blot under denatured conditions, suggested post-translational modifications that affect antibody binding. This aligns with altered efficiency at proteolytic cleavage sites indicated in the targeted MS experiment. These findings highlight that post-translational modifications extend to astrocytes, affecting their functions. CKB and the creatine-phosphocreatine cycle play crucial roles in energy buffering, securing constant ATP availability. Reduced ATP in astrocytes can disrupt ATP-dependent processes, such as the glutamate-glutamine cycle. Post-translational modifications in CKB and astrocyte dysfunction may disturb homeostasis, driving excitotoxicity in the AD brain. CKB and its activity emerge as potential biomarkers for monitoring early-stage energy deficits in AD.
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportsupported by repository but incomplete data and/or metadata
PrimarySubmitterDavid Kotol
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-22 21:31:32ID requested
12024-05-21 16:14:50announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: brain creatine kinase, CKB, Alzeheimer's disease, Dementia, energy-deficit
Contact List
Fredrik Edfors
contact affiliationKTH, Science for Life Laboratory, Solna, Sweden
contact emailfredrik.edfors@scilifelab.se
lab head
David Kotol
contact affiliationKTH, Science for Life Laboratory, Solna, Sweden
contact emaildavid.kotol@scilifelab.se
dataset submitter
Full Dataset Link List
Panorama Public dataset URI