{"doi":"10.3389/fnagi.2021.765259","title":"Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias","abstract":"Glycosylation, the process of adding glycans (i.e., sugars) to proteins, is the most abundant post-translational modification. N-glycosylation is the most common form of glycosylation, and the N-glycan moieties play key roles in regulating protein functions and many other biological processes. Thus, identification and quantification of N-glycome (complete repertoire of all N-glycans in a sample) may provide new sources of biomarkers and shed light on health and disease. To date, little is known about the role of altered N-glycome in Alzheimer's Disease and Alzheimer's Disease-related Dementias (AD/ADRD). The current study included 45 older adults who had no cognitive impairment (NCI) at baseline, followed and examined annually, and underwent brain autopsy after death. During about 12-year follow-up, 15 developed mild cognitive impairment (MCI), 15 developed AD, and 15 remained NCI. Relative abundances of N-glycans in serum at 2 time points (baseline and proximate to death, ∼12.3 years apart) and postmortem brain tissue (dorsolateral prefrontal cortex) were quantified using MALDI-TOF-MS. Regression models were used to test the associations of N-glycans with AD/ADRD phenotypes. We detected 71 serum and 141 brain N-glycans, of which 46 were in common. Most serum N-glycans had mean fold changes less than one between baseline and proximate to death. The cross-tissue N-glycan correlations were weak. Baseline serum N-glycans were more strongly associated with AD/ADRD compared to change in serum N-glycans over time and brain N-glycans. The N-glycan associations were observed in both AD and non-AD neuropathologies. To our knowledge, this is the first comprehensive glycomic analysis in both blood and brain in relation to AD pathology. Our results suggest that altered N-glycans may serve as mechanistic biomarkers for early diagnosis and progression of AD/ADRD.","journal":"Frontiers in Aging Neuroscience","year":2021,"id":177854,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9354,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":270104,"name":"Zhiguang Huo","orcid":"0000-0002-8032-4392","position":1,"is_corresponding":false},{"id":309256,"name":"Jingyun Yang","orcid":"0000-0002-3495-3710","position":2,"is_corresponding":false},{"id":722834,"name":"Helena Palma‐Gudiel","orcid":"0000-0002-4961-8077","position":3,"is_corresponding":false},{"id":287751,"name":"Patricia A. Boyle","orcid":"0000-0002-3245-3456","position":4,"is_corresponding":false},{"id":7426,"name":"Julie A. Schneider","orcid":"0000-0002-9482-1752","position":5,"is_corresponding":false},{"id":778,"name":"David A. Bennett","orcid":"0000-0003-3689-554X","position":6,"is_corresponding":false},{"id":564457,"name":"Jinying Zhao","orcid":"0000-0003-3243-2660","position":7,"is_corresponding":false},{"id":12926,"name":"Lei Yu","orcid":"0000-0002-7176-1152","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:36.112170Z","pmid":"34776937","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}