# MALDI imaging of glial scar-forming glycans in Alzheimers disease

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $264,750

## Abstract

Alzheimer’s disease (AD) is a dementing disorder characterized by the pathological accumulation of beta-
amyloid (Ab) and hyperphosphorylated tau neurofibrillary tangles (NFTs). Recent evidence suggests a close
topographical relationship P-tau accumulation and neuronal loss with changes in gene expression mediating
chondroitin sulfate (CS) and dermatan sulfate (DS) glycosaminoglycan (GAG) metabolism. CS/DS-GAGs are
extracellular polyanionic polymers that have previously been shown to interact with P-tau and Ab, although the
underlying molecular mechanisms and physiological consequences for these interactions remain unclear.
Studies that investigate the relationship between changes in brain CS/DS-GAGs and AD-associated pathological
endpoints are therefore necessary to elucidate a novel role for glycans in the clinical pathogenesis of AD.
 The biological functions of extracellular CS/DS-GAGs are highly influenced by the incorporation of sulfated
disaccharide isomers (0S-, 4S-, 6S-, 2S6S-, 4S6S-CS and 2S4S-DS) into the glycan matrix lattices. Often
referred to as the biological “sulfation code”, the relative abundance of non-, mono- and di-sulfated CS/DS
isomers is believed to control ion buffering, protein-glycan interactions, and neurocircuit synapse stability in the
brain. Using state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS), our Preliminary
Data show a significant increase in the relative abundance of glial scar-associated isomers (6S- and 4S6S-CS)
within the medial frontal gyrus of patients with AD compared to non-AD controls. Moreover, these glial scar-
associated CS isomers positively correlate with the abundance of P-tau from the same brain tissue, suggesting
that changes in the brain CS/DS-GAG sulfation code could serve as a novel and unexplored player in the
progression of AD. Specifically, we hypothesize that the increase in glial-scarring CS/DS-GAGs may represent
1) a physiological CNS barrier to isolate P-tau neuropathology from the healthy brain tissue and 2) a repressor
of neurogenesis and source of cellular toxicity, potentially exacerbating neurodegeneration in AD. Here, we
propose to uncover the spatial distribution of CS/DS isomers with the underlying cellular (neuronal, glial) and
pathological (P-tau, Ab) tissue pathology by coupling matrix assisted laser desorption ionization (MALDI) mass
spectrometry imaging (IMS) of CS/DS isomers with histochemical protein labeling using advanced High
Definition Imaging (HDI) overlay technology. Deciphering a relationship between maladaptive changes in the
brain CS/DS-GAG sulfation code and development of AD pathology is a novel and unexplored area of glycan-
based neuroscience with the potential to revolutionize the field of AD research.

## Key facts

- **NIH application ID:** 10300280
- **Project number:** 1R21AG074152-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kimberly Michele Alonge
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $264,750
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300280

## Citation

> US National Institutes of Health, RePORTER application 10300280, MALDI imaging of glial scar-forming glycans in Alzheimers disease (1R21AG074152-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10300280. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*