TOMM40 polymorphism is associated with resting-state functional MRI results in patients with Alzheimer's disease
Xuewen Xiao1, Jingya Wei1, Weiwei Zhang1,2
1Departments of Neurology.
Objective:
Translocase of outer mitochondrial membrane 40 (TOMM40) encodes translocase of the outer mitochondrial membrane (TOM), which is associated with mitochondrial dysfunction in Alzheimer's disease (AD). TOMM40 rs157581-G has been reported to increase susceptibility to AD. However, the effect of TOMM40 rs157581-G in resting-state functional MRI (rs-fMRI) on AD has not been studied. Therefore, we aimed to investigate the role of TOMM40 rs157581-G on rs-fMRI results in AD patients.
Methods:
Twenty-four AD patients were divided into two groups based on TOMM40 rs157581-G status, and clinical and imaging data were compared between the groups.
Results:
TOMM40 rs157581-G carriers of AD showed decreased regional homogeneity in the left precuneus and decreased amplitude of low-frequency fluctuations in the bilateral temporal poles compared with noncarriers of AD. TOMM40 rs157581-G carriers of AD also showed increased functional connectivity between the right middle occipital gyrus and the left supramarginal gyrus and decreased connectivity between the left superior occipital gyrus and the right transverse temporal gyrus in comparison with TOMM40 rs157581-G noncarriers.
Conclusion:
We analyzed rs-fMRI characteristics of TOMM40 rs157581-G carriers of AD for the first time, which suggest that TOMM40 rs157581-G plays a harmful role in AD patients.
Insights
The TOMM40 rs157581-G gene variant is linked to altered brain activity in Alzheimer's disease (AD) patients. This study reveals its harmful role, impacting functional connectivity and brain regions crucial for AD progression.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Mitochondrial dysfunction is implicated in Alzheimer's disease (AD).
- The TOMM40 rs157581-G gene variant is associated with increased AD susceptibility.
- The impact of TOMM40 rs157581-G on resting-state functional MRI (rs-fMRI) in AD remains uninvestigated.
Purpose of the Study:
- To investigate the role of the TOMM40 rs157581-G variant in Alzheimer's disease.
- To analyze the effects of TOMM40 rs157581-G on rs-fMRI findings in AD patients.
Main Methods:
- Twenty-four AD patients were categorized into two groups based on TOMM40 rs157581-G carrier status.
- Clinical and imaging data, specifically rs-fMRI, were compared between the groups.
Main Results:
- TOMM40 rs157581-G carriers exhibited reduced regional homogeneity in the left precuneus and decreased amplitude of low-frequency fluctuations in bilateral temporal poles.
- Increased functional connectivity was observed between the right middle occipital gyrus and left supramarginal gyrus in carriers.
- Decreased functional connectivity was noted between the left superior occipital gyrus and right transverse temporal gyrus in carriers.
Conclusions:
- This study provides the first analysis of rs-fMRI characteristics in TOMM40 rs157581-G carriers with AD.
- The findings suggest that the TOMM40 rs157581-G variant plays a detrimental role in Alzheimer's disease pathogenesis.
