Human brain glycoform co-regulation network and glycan modification alterations in Alzheimer's disease
Zhang, Q.; Ma, C.; Chin, L.-S.; Pan, S.; Li, L.
Show abstract
Despite the importance of protein glycosylation to brain health, current knowledge of glycosylated proteoforms or glycoforms in human brain and their alterations in Alzheimers disease (AD) is limited. Here, we present a new paradigm of proteome-wide glycoform profiling study of human AD and control brains using intact glycopeptide-based quantitative glycoproteomics coupled with systems biology. Our study identified over 10,000 human brain N-glycoforms from nearly 1200 glycoproteins and uncovered disease signatures of altered glycoforms and glycan modifications, including reduced sialylation and N-glycan branching as well as elevated mannosylation and N-glycan truncation in AD. Network analyses revealed a higher-order organization of brain glycoproteome into networks of co-regulated glycoforms and glycans and discovered glycoform and glycan modules associated with AD clinical phenotype, amyloid-{beta} accumulation, and tau pathology. Our findings provide novel insights and a rich resource of glycoform and glycan changes in AD and pave the way forward for developing glycosylation-based therapies and biomarkers for AD.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication 95%
- Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer's disease retina 94%
- Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases 94%
Similar papers in this journal
- Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy 95%
- Cerebrospinal fluid total tau levels indicate aberrant neuronal plasticity in Alzheimer’s disease 94%
- APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology 94%
Similar papers in this journal
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity 93%
- Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's Disease 92%
- Sustained TREM2 stabilization accelerates microglia heterogeneity and Abeta pathology in a mouse model of Alzheimer s disease 92%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.