Genetic Factors Implicated in the Investigation of Possible Connections between Alzheimer’s Disease and Primary Open Angle Glaucoma
Abstract
:1. Introduction
2. Overview of Alzheimer’s Disease and Glaucoma
2.1. Alzheimer’s Disease
2.2. Glaucoma
3. Background of Connections between Alzheimer’s Disease and Glaucoma
4. Genetic Factors Relevant to Alzheimer’s Disease and Primary Open Angle Glaucoma
5. Implications of Genetic Connections between Alzheimer’s Disease and Glaucoma
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Name | Location | Protein Product | Function | Pathogenic Mutation | Association with AD | Association with POAG |
---|---|---|---|---|---|---|---|
AGBL2 | ATP/GTP-binding protein-like 2 | 11p11.2 | Cytosolic carboxypeptidase 2 (CCP2) enzyme | Catalyzes post-translational modification of ɑ-tubulin subunit | rs11604825 rs11602395 | Microtubular axonal transport alteration | IOP elevation |
MAPT | Microtubule associated protein tau | 17q21.31 | Microtubule-associated protein tau (MAPT) | Encodes tau proteins and other mRNA products | Post-translational alternative splicing and modification | Tau structure isoform variations | Misbalance in glaucomatous RGC axons |
SPI1 | Spi-1 proto-oncogene | 11p11.2 | PU.1 erythroblast transformation specific (ETS) transcription factor | Promotes gene expression of hematopoietic cell lineages | 28 SNP’s | Microglia activation | Microglia activation, IOP elevation |
CELF1 | CUG triplet repeat, RNA binding protein 1 (CUGBP) embryonic lethal abnormal vision (Elav)-like family member 1 | 11p11.2 | CELF/BRUNOL protein | Regulates pre-mRNA splicing and mRNA expression | rs4752845 rs34958982 rs66749409 rs12798346 rs56400411 | Alternative splicing of tau protein | IOP elevation |
FAM180B | Family with sequence similarity 180 member B | 11p11.2 | Family with sequence similarity 180 member B | Presently unknown function | rs11605348 | Expressed at higher levels in brain | IOP elevation |
MTCH2 | Mitochondrial carrier 2 | 11p11.2 | Solute carrierfamily 25 (SLC25) family nuclear-encoded mitochondrial transporters | Involved in apoptotic pathway via recruitment of Bcl-2 family BID protein | rs4752856 rs4752856 rs4752856 | Disrupts mitochondrial motility, metabolism, and function | IOP elevation |
MYBPC3 | Myosin binding protein C3 | 11p11.2 | Cardiac isoform of myosin binding protein C (MyBP-C) | Regulates cardiac striated muscle contraction | rs2856661 | May affect axonal growth and synaptic development | IOP elevation |
NDUFS3 | NADH:ubiquinone oxidoreductase core subunit S3 | 11p11.2 | Iron-sulfur protein (IP) component in mitochondrial NADH:ubiquinone oxidoreductase (complex I) | Involved in mitochondrial electron transport chain and cellular functions | rs2030166 rs2030166 | Increased levels in early stages of mild cognitive impairment | IOP elevation |
PSMC3 | Proteasome 26S subunit, ATPase 3 | 11p11.2 | 26S proteasome | Involved in ubiquitin-proteasome degradation system | rs11600581 | Increased cellular proteotoxic stress | IOP elevation |
PTPMT1 | Protein tyrosine phosphatase mitochondrial 1 | 11p11.2 | Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 | Involved in mitochondrial metabolic pathways and embryogenesis | rs56400411 rs7945473 | Mitochondrial dysfunction | IOP elevation |
RAPSN | Receptor associated protein of the synapse | 11p11.2 | Receptor-associated protein of the synapse | Anchors postsynaptic nicotinic acetylcholine receptors | rs35705029 | Acetylcholine neurotransmitter signal alteration | IOP elevation |
SLC39A13 | Solute carrier family 39 member 13 | 11p11.2 | Zinc transporter transmembrane protein | Facilitates zinc transport across membranes | rs755554 | Disturbance of zinc homeostasis | IOP elevation |
CADM2 | Cell adhesion molecule 2 | 3p12.1 | Synaptic cell adhesion molecule 1 (SynCAM) | Interacts with cytoskeletal proteins for cellular support and structure | r71316816 rs13101042 rs2220243 | Impaired synaptic adhesion and maintenance | Expressed almost exclusively in brain and retina and found to have altered expression throughout all stages of glaucoma |
APP | Amyloid beta precursor protein | 21q21.3 | Amyloid precursor protein (APP) | Acts as a transmembrane cell surface receptor and regulates neuronal functions | rs59892895 | Abnormal cleavage forms β-amyloid plaques | Increased abnormal expression in glaucoma models |
APOE | Apolipoprotein E | 19q13.32 | Apolipoprotein E | Maintains lipid metabolism and balance in circulatory and peripheral systems | ε4 allele | Increased risk for disease, increased amount of β-amyloid plaques | Reduced risk for disease, decrease activation of microglia |
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Kuang, G.; Salowe, R.; O’Brien, J. Genetic Factors Implicated in the Investigation of Possible Connections between Alzheimer’s Disease and Primary Open Angle Glaucoma. Genes 2023, 14, 338. https://doi.org/10.3390/genes14020338
Kuang G, Salowe R, O’Brien J. Genetic Factors Implicated in the Investigation of Possible Connections between Alzheimer’s Disease and Primary Open Angle Glaucoma. Genes. 2023; 14(2):338. https://doi.org/10.3390/genes14020338
Chicago/Turabian StyleKuang, Grace, Rebecca Salowe, and Joan O’Brien. 2023. "Genetic Factors Implicated in the Investigation of Possible Connections between Alzheimer’s Disease and Primary Open Angle Glaucoma" Genes 14, no. 2: 338. https://doi.org/10.3390/genes14020338
APA StyleKuang, G., Salowe, R., & O’Brien, J. (2023). Genetic Factors Implicated in the Investigation of Possible Connections between Alzheimer’s Disease and Primary Open Angle Glaucoma. Genes, 14(2), 338. https://doi.org/10.3390/genes14020338