# Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $702,916

## Abstract

The molecular and cellular mechanism involved in the etiology of Alzheimer’s disease (AD) is still not fully
understood. The risk factors underlying the heterogeneity and multifactorial nature of AD may include genetic
background, environment, life styles, and the status of key molecules, i.e. amyloid, tau, ApoE, TREM2, biometals
(Ca2+, Mg2+, Cu2+, etc.) and others. The goal of this study is to explore the potential role of Mg2+ in neuronal cell
protection under AD-like pathological conditions and the underlying molecular mechanisms. The rationale is
that 1) Mg2+-deficiency is correlated to aging and AD pathology, and 2) elevated brain Mg2+ enhances learning
and memory, reduces neuroinflammation, and protects cognitive functions and synaptic plasticity in AD animal
models. Prior studies revealed that brain and serum Mg2+ levels are significantly lower in patients with AD than
in age-matched normal subjects. Moreover, Mg2+ elevation enhanced learning and memory in aged rats,
prevented synaptic loss and reversed cognitive deficits in APP/PS1 AD mice and streptozotocin-induced
sporadic AD rat model, as well as reduced neuroinflammation in brain injury and APP/PS1 AD model. In light of
these findings, dyshomeostasis of Mg2+ in the brain is believed to be involved in the progression of AD. In
addition, Mg2+ itself is a nature antioxidant, an antagonist of Ca2+, and an essential cofactor for ATP, nucleic
acids and over 600 enzyme systems. Thus collectively, the hypothesis is that Mg2+ protects neurons by serving
as an antioxidant to reduce oxidative stress, inflammation, and synaptic loss. Aim 1 is to examine efficacy and
mechanism of Mg2+ on reducing oxidative stress and neuroinflammation. Aim 2 is to examine efficacy and
mechanism of Mg2+ on inhibiting Aβ-induced synaptic loss and dysfunction. First, the mechanisms of how Mg2+
enters the cells and reduces Aβ-induced oxidative stress and inflammation in vitro will be elucidated and followed
by validation of its efficacy on oxidative stress & inflammation suppression in AD animal model. Next, the
mechanisms of how Mg2+ protects neurons from Aβ-induced synaptic loss and dysfunction, as well as Aβ-
induced tau hyperphosphorylation and mitochondrial fragmentation in vitro. Last, the efficacy of Mg2+ on synaptic
plasticity and cognitive deficits amelioration in AD animal model will be validated.

## Key facts

- **NIH application ID:** 10418762
- **Project number:** 5R01AG064798-04
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Donghui Zhu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $702,916
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418762

## Citation

> US National Institutes of Health, RePORTER application 10418762, Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease (5R01AG064798-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418762. Licensed CC0.

---

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