# Comprehensive Characterization of Glycosylation Alterations in Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $664,010

## Abstract

Project Summary
Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is growing in prevalence despite
decades of investment in the research and development of diagnostics and therapeutics. Because of the high
healthcare burden and devastating effects of AD on cognitive function and quality of life, early biomarkers of
disease and interventions to prevent and treat AD are a public health priority. The search for biomarkers and
treatments has turned to glycobiology, the study of complex sugars attached to proteins and lipids. The post-
translational glycosylation of proteins and lipids plays a role in a number of critical biological processes
including cell-to-cell communication and signaling, and protein structure and function. Recently, major
alterations in glycosylation have been documented in the brains, cerebrospinal fluid, and blood of AD patients
even before the onset of advanced cognitive decline. Glycosylation is likely to be causally involved in AD, thus
measuring glycosylation in blood is a promising strategy for discovering early biomarkers. Apolipoprotein E
(ApoE) is the single greatest genetic risk factor for AD. Carriers of the ApoE4 isoform are 4-12 times more
likely to develop AD depending on the number of copies of ApoE4, and develop the disease as many as 20
years earlier. ApoE is a glycosylated protein, and nearly all of the proteins, carriers, and receptors involved in
its metabolism are also glycosylated. The structure of ApoE heavily influences its functionality. Glycosylation is
known to alter protein structure yet neither the glycosylation of ApoE, nor the overall glycosylation in the brain
and in the blood have been adequately characterized in Alzheimer’s disease patients because the lack of
precise analytical tools for measuring glycosylation has been a technological barrier to progress. Our group
has pioneered the development of advanced and sensitive liquid chromatography-mass spectrometry methods
as tools to precisely measure glycosylation alterations across hundreds of lipids and proteins simultaneously.
Our method is rapid-throughput and can monitor the site-specificity, structure specificity, and linkage specificity
of all attached glycans in hundreds of clinical samples with high reproducibility, accuracy and sensitivity. The
three specific aims of this project are to map the global glycosylation alterations in the brains and blood of
Alzheimer’s disease patients compared with controls, to characterize the site-specific changes in glycosylation
of ApoE, and to document the effects of glycosylation changes on critical pathways involved in Alzheimer’s
disease pathology. Importantly, the differences in glycosylation in AD will be mapped within each ApoE
genotype, which will enable the discovery of precision medicine based solutions. Successful completion of this
project will lead to the development of new glycosylation-based biomarkers for the early detection of
Alzheimer’s disease and ApoE-specif...

## Key facts

- **NIH application ID:** 9974465
- **Project number:** 5R01AG062240-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** LEE-WAY JIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $664,010
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974465

## Citation

> US National Institutes of Health, RePORTER application 9974465, Comprehensive Characterization of Glycosylation Alterations in Alzheimer's Disease (5R01AG062240-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974465. Licensed CC0.

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