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Updated: Nov 25, 2025
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Polymorphism in the MAGI2 Gene Modifies the Effect of Amyloid β on Neurodegeneration
Hang-Rai Kim1,2,3, Taeyeop Lee1,4, Jung K Choi5
1Graduate School of Medical Science & Engineering.
Introduction:
A weak association between amyloid β (Aβ) deposition and neurodegeneration biomarkers, such as brain atrophy, has been repeatedly reported in a subset of patients with Alzheimer disease, suggesting individual differences in response to Aβ deposition.
Methods:
Here, we performed a genome-wide interaction study to identify single-nucleotide polymorphism (SNP) that modify the effect of Aβ (measured by 18F-florbetapir positron emission tomography) on brain atrophy (measured by cortical thickness using magnetic resonance imaging). We used magnetic resonance imaging, positron emission tomography, cerebrospinal fluid, and genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database [discovery cohort, ADNI-GO/2 (n=723) and replication cohort, ADNI-1 (n=129)].
Results:
We identified a genome-wide suggestive interaction of rs3807779 SNP (β=-0.14, SE=0.029, P=9.08×10-7) in the discovery cohort. The greater dosage of rs3807779 SNP increased the detrimental effect of Aβ deposition on cortical thickness. In replication analyses, the congruent results were replicated to confirm our findings. Furthermore, rs3807779 SNP augmented the detrimental effect of Aβ deposition on cognitive function. Genetic profiling showed that rs3807779 has chromatin interactions with the promoter region of MAGI2 gene, suggesting its association with MAGI2 expression.
Conclusions:
These findings demonstrate that subjects carrying the rs3807779 SNP are more susceptible to Aβ-related neurodegeneration.
Insights
A specific gene variant, rs3807779, increases susceptibility to Alzheimer's disease neurodegeneration caused by amyloid-beta deposition. This single-nucleotide polymorphism (SNP) exacerbates brain atrophy and cognitive decline in affected individuals.
Area of Science:
- Neuroscience
- Genetics
- Alzheimer's Disease Research
Background:
- Alzheimer's disease (AD) exhibits variable patient responses to amyloid-beta (Aβ) deposition, indicating underlying genetic modifiers.
- Brain atrophy and neurodegeneration biomarkers show a weak association with Aβ in some AD patients.
Purpose of the Study:
- To conduct a genome-wide interaction study to identify single-nucleotide polymorphisms (SNPs) that modify the impact of Aβ on brain atrophy.
- Investigate genetic factors influencing individual susceptibility to Aβ-induced neurodegeneration in Alzheimer's disease.
Main Methods:
- Utilized genome-wide interaction analysis on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.
- Combined magnetic resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid (CSF), and genetic data from discovery (n=723) and replication (n=129) cohorts.
- Assessed Aβ deposition via 18F-florbetapir PET and brain atrophy via cortical thickness from MRI.
Main Results:
- Identified a genome-wide suggestive interaction with rs3807779 SNP, which intensifies the detrimental effect of Aβ on cortical thickness.
- Replicated findings confirmed that rs3807779 SNP exacerbates Aβ's negative impact on cognitive function.
- Genetic profiling indicated rs3807779 SNP interacts with the MAGI2 gene promoter, suggesting a role in MAGI2 expression.
Conclusions:
- Subjects with the rs3807779 SNP are demonstrably more vulnerable to neurodegeneration associated with Aβ deposition.
- This study highlights rs3807779 as a key genetic modifier influencing Alzheimer's disease progression.
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