# Creating a region- specific biomolecular atlas of the brain of Alzheimer’s disease

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $747,773

## Abstract

PROJECT SUMMARY
 Many diseases of aging, including Alzheimer’s disease (AD) and AD related dementia, have been linked
with significant metabolic changes that are regulated by diverse molecular classes. Nodes of the aging- and
AD-associated metabolic signature include: (i) General proteomic profile as reflecting changes in protein
homeostasis and/or an ongoing neurodegenerative event; (ii) Glycosylation of glycoproteins, as reflecting
changes in engagement and trafficking along the secretory pathway, as well as “post-delivery” processing cell-
surface glycoproteins; and (iii) Biological membrane lipid composition and general bioactive lipid metabolism.
 Several studies have shown changes in brain metabolism are not uniform throughout AD progression, with
parietal, posterior temporal, and anterior occipital lobes most severely affected. Because of this, broad
conclusions about the AD brain following analysis that does not include spatial information may be painting an
incomplete picture of AD pathogenesis. Due to the complexity of the brain, spatial distribution as well as
functional integrations of the above nodes are warranted to understand both aging of the brain and AD
pathophysiology. To perform a more comprehensive analysis of region-specific molecular pattern changes in
the AD brain, we propose to employ matrix-assisted laser desorption/ionization mass spectrometric imaging
(MALDI MSI) technology to examine spatial distribution changes of several molecular classes in animal models
of AD as well as postmortem brain tissue of late-onset AD (LOAD) patients.
 The GENERAL HYPOTHESIS of this research is that alteration in the molecular pattern of various
biologically relevant molecular classes can reflect or influence the onset and progression of AD. Aim 1 will
map region-specific glycan and glycoprotein expression pattern changes in the whole brain tissue sections of
AD mouse models and LOAD patient tissue samples. We will create an atlas of the glycoproteome and
illuminating changes in glycosylation that could be key in understanding AD pathogenesis. Aim 2 will map
lipidome and unsaturated lipid isomers and changes in metabolic signature in the whole brain tissue sections
of AD mouse models and LOAD patient tissue samples. The use of innovative double-bond localization
chemistry will expand our current understanding of the AD lipidome, revealing a molecular map of not just lipid
classes, but specific lipid isomers within the AD brain. Aim 3 will develop technology- and computationally-
driven approaches for biomolecule validation, co-localization, and multidimensional correlation. Our proposed
machine learning algorithms will enable simultaneous and region-specific correlation of multiple classes of
molecules. Our collaborative team’s orthogonal research foci and interdisciplinary expertise will enable us to
generate novel mechanistic and translational data that will inform the research community on the progression
of aging and AD. The mechanist...

## Key facts

- **NIH application ID:** 10889101
- **Project number:** 5R01AG078794-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** LINGJUN LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,773
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889101

## Citation

> US National Institutes of Health, RePORTER application 10889101, Creating a region- specific biomolecular atlas of the brain of Alzheimer’s disease (5R01AG078794-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10889101. Licensed CC0.

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