PXD050060

PXD050060 is an original dataset announced via ProteomeXchange.

Title	Brain Creatine Kinase as a biomarker for Alzheimer’s disease
Description	The 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.
HostingRepository	PanoramaPublic
AnnounceDate	2024-07-03
AnnouncementXML	Submission_2024-07-03_19:16:45.138.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	David Kotol
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-22 21:31:32	ID requested
1	2024-05-21 16:14:50	announced
⏵ 2	2024-07-03 19:16:46	announced	: Added PubMed Id

Zheng T, Kotol D, Sj, ö, berg R, Mitsios N, Uhl, é, n M, Zhong W, Edfors F, Mulder J, Characterization of reduced astrocyte creatine kinase levels in Alzheimer's disease. Glia, 72(9):1590-1603(2024) [pubmed]

submitter keyword: brain creatine kinase, CKB, Alzeheimer's disease, Dementia, energy-deficit

Fredrik Edfors
contact affiliation	KTH, Science for Life Laboratory, Solna, Sweden
contact email	fredrik.edfors@scilifelab.se
lab head
David Kotol
contact affiliation	KTH, Science for Life Laboratory, Solna, Sweden
contact email	david.kotol@scilifelab.se
dataset submitter

Panorama Public dataset URI