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Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias

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,...

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Autores principales: Yu, Lei, Huo, Zhiguang, Yang, Jingyun, Palma-Gudiel, Helena, Boyle, Patricia A., Schneider, Julie A., Bennett, David A., Zhao, Jinying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579010/
https://www.ncbi.nlm.nih.gov/pubmed/34776937
http://dx.doi.org/10.3389/fnagi.2021.765259
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author Yu, Lei
Huo, Zhiguang
Yang, Jingyun
Palma-Gudiel, Helena
Boyle, Patricia A.
Schneider, Julie A.
Bennett, David A.
Zhao, Jinying
author_facet Yu, Lei
Huo, Zhiguang
Yang, Jingyun
Palma-Gudiel, Helena
Boyle, Patricia A.
Schneider, Julie A.
Bennett, David A.
Zhao, Jinying
author_sort Yu, Lei
collection PubMed
description 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.
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spelling pubmed-85790102021-11-11 Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias Yu, Lei Huo, Zhiguang Yang, Jingyun Palma-Gudiel, Helena Boyle, Patricia A. Schneider, Julie A. Bennett, David A. Zhao, Jinying Front Aging Neurosci Neuroscience 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. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8579010/ /pubmed/34776937 http://dx.doi.org/10.3389/fnagi.2021.765259 Text en Copyright © 2021 Yu, Huo, Yang, Palma-Gudiel, Boyle, Schneider, Bennett and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Yu, Lei
Huo, Zhiguang
Yang, Jingyun
Palma-Gudiel, Helena
Boyle, Patricia A.
Schneider, Julie A.
Bennett, David A.
Zhao, Jinying
Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
title Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
title_full Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
title_fullStr Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
title_full_unstemmed Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
title_short Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
title_sort human brain and blood n-glycome profiling in alzheimer’s disease and alzheimer’s disease-related dementias
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579010/
https://www.ncbi.nlm.nih.gov/pubmed/34776937
http://dx.doi.org/10.3389/fnagi.2021.765259
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