Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions
Abstract
:1. Introduction
2. Materials and Methods
2.1. ROSMAP Cohort
2.1.1. APOE and TMEM106B Expression Levels from Human Dorsolateral Prefrontal Cortices
2.1.2. APOE and TMEM106B Protein Levels from Human Dorsolateral Prefrontal Cortices
2.1.3. Genotype Data from ROSMAP
2.2. The Mayo Clinic Cohort
2.3. Animals
2.3.1. Unilateral Entorhinal Cortex Lesions (ECL)
2.3.2. RNA Extraction from Mice Hippocampi
2.3.3. Tmem106b Expression Levels in ECL Mice
2.4. Statistical Analyses
3. Results
3.1. Human Brains
3.1.1. APOE mRNA Levels Are Strongly Influenced by TMEM106B Genetic Variants
3.1.2. TMEM106B mRNA Levels Are not Influenced by Cis-Acting Polymorphisms
3.1.3. TMEM106B Protein Levels Are Influenced by Nearby Genetic Variants
3.1.4. The T185S Coding SNP Correlates with Lower TMEM106B Protein Levels and Lower APOE mRNA Levels
3.1.5. TMEM106B mRNA Levels Are Elevated in AD Temporal Cortices Compared to Brain Tissues from Cognitively Unimpaired Individuals
3.1.6. TMEM106B Protein Levels Are Elevated in Individuals Affected with Mild Cognitive Impairment and Alzheimer’s Disease Compared to Cognitively Unimpaired Individuals
3.2. Animals
Tmem106b Levels Are Reduced during the Hippocampal Deafferentation Phase and Reach Peak Levels during the Reinnervation Phase in Entorhinal Cortex Lesioned Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SNP | Location | Disease | Ref. |
---|---|---|---|
rs3173615 | Exon 6 | FTL-TDP, CTE, PD | [30,31,32,33] |
(T185S) | |||
rs13237518 | intron | AD, T2D | [34,35] |
rs1548884 | 3′UTR | ||
rs1990622 | downstream | FTLD-TDP, ALS, AD, PD, HipScl | [33,36,37,38,39,40,41,42,43,44,45,46] |
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Picard, C.; Miron, J.; Poirier, J. Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions. Genes 2024, 15, 416. https://doi.org/10.3390/genes15040416
Picard C, Miron J, Poirier J. Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions. Genes. 2024; 15(4):416. https://doi.org/10.3390/genes15040416
Chicago/Turabian StylePicard, Cynthia, Justin Miron, and Judes Poirier. 2024. "Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions" Genes 15, no. 4: 416. https://doi.org/10.3390/genes15040416
APA StylePicard, C., Miron, J., & Poirier, J. (2024). Association of TMEM106B with Cortical APOE Gene Expression in Neurodegenerative Conditions. Genes, 15(4), 416. https://doi.org/10.3390/genes15040416