Complexity of Sex Differences and Their Impact on Alzheimer’s Disease
Abstract
:1. Introduction
2. Alzheimer’s Disease
3. Biological Sex Differences
3.1. Brain Morphology
3.2. Sex Hormones
3.3. Aging
3.4. Sex Differences in Alzheimer’s Disease
4. Microglia
4.1. Male and Female Microglia
4.2. Microglia and Estrogen
4.3. Microglia, Neuroinflammation and Alzheimer’s Disease
5. Common Model Systems for Studying Alzheimer’s Disease
5.1. Mouse Models
5.2. In Vitro Models
5.2.1. 2D Cellular Models
5.2.2. Cerebral Organoids
6. Discussion
Author Contributions
Funding
Conflicts of Interest
References
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SNP ID | Gene | Variant | Frequency | Function | Brain Expression |
---|---|---|---|---|---|
rs3752246 | ABCA7 | G > C/C > T | G = 0.15755 (C = 0.84245) | Lipid homeostasis | Neurons, astrocytes, microglia and oligodendrocytes |
rs3764650 | ABCA7 | T > G | G = 0.102719 (T = 0.897281) | Lipid homeostasis | Neurons, astrocytes, microglia and oligodendrocytes |
rs1800764 | ACE | C > G/C > T | C = 0.481027 (T = 0.518973) | Blood pressure and electrolyte balance | Neurons, microglia and oligodendrocytes |
rs442495 | ADAM10 | T > C/T > G | C = 0.40762 (T = 0.59238) | Lipid transport and phagocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs7412 | APOC1 | C > T | T = 0.083116 (C = 0.916884) | Lipid transport | Microglia, astrocytes and neurons |
rs429358 | APOC1 | T > C | C = 0.074418 (T = 0.925582) | Lipid transport | Microglia, astrocytes and neurons |
rs4663105 | BIN1 | A > C | C = 0.44298 (A = 0.55702) | Endocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs744373 | BIN1 | A > C/A > G/A > T | G = 0.297771 (A = 0.702229) | Endocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs9381563 | CD2AP | C > A/C > G/C > T | C = 0.39767 (T = 0.60233) | Cytoskeleton regulation | Microglia, neurons, astrocytes and oligodendrocytes |
rs9349407 | CD2AP | G > C | C = 0.24780 (G = 0.75220) | Cytoskeleton regulation | Microglia, neurons, astrocytes and oligodendrocytes |
rs10948363 | CD2AP | A > G | G = 0.24596 (A = 0.75404) | Cytoskeleton regulation | Microglia, neurons, astrocytes and oligodendrocytes |
rs1354106 | CD33 | T > G | G = 0.34719 (T = 0.65281) | Cell adhesion and immune cell homeostasis | Microglia |
rs3865444 | CD33 | C > A | A = 0.302324 (C = 0.697676) | Cell adhesion and immune cell homeostasis | Microglia |
rs12459419 | CD33 | C > A/C > G/C > T | T = 0.26380 (C = 0.73620) | Cell adhesion and immune cell homeostasis | Microglia |
rs4845378 | CHRNB2 | G > A/G > T | T = 0.08354 (G = 0.91646) | Ion transport | Neurons, oligodendrocytes and astrocytes, microglia |
rs11136000 | CLU | T > A/T > C | C = 0.607739 (T = 0.392261) | Apoptosis, complement and immunity | Astrocytes, microglia, neurons and oligodendrocytes |
rs9331896 | CLU | C > A/C > G/C > T | C = 0.42127 (T = 0.57873) | Apoptosis, complement and immunity | Astrocytes, microglia, neurons and oligodendrocytes |
rs1532278 | CLU | T > A/T > C | T = 0.374146 (C = 0.625854) | Apoptosis, complement and immunity | Astrocytes, microglia, neurons and oligodendrocytes |
rs4236673 | CLU | A > C/A > G | A = 0.33623 (G = 0.66377) | Apoptosis, complement and immunity | Astrocytes, microglia, neurons and oligodendrocytes |
rs3818361 | CR1 | A > C/A > G | A = 0.201980 (G = 0.798020) | Complement and immunity | Oligodendrocytes and microglia |
rs6656401 | CR1 | A > G/A > T | A = 0.179434 (G = 0.820566) | Complement and immunity | Oligodendrocytes and microglia |
rs4844609 | CR1 | A > G/A > T | A = 0.021785 (T = 0.978215) | Complement and immunity | Oligodendrocytes and microglia |
rs1064039 | CST3 | C > G/C > T | T = 0.19579 (C = 0.80421) | Protease inhibitor | Astrocytes, oligodendrocytes and microglia |
rs11771145 | EPHA1 | G > A/G > T | A = 0.351605 (G = 0.648395) | Angiogenesis and cell adhesion | Neurons and microglia |
rs11763230 | EPHA1 | C > T | T = 0.20866 (C = 0.79134) | Angiogenesis and cell adhesion | Neurons and microglia |
rs11767557 | EPHA1 | T > A/T > C | C = 0.194037 (T = 0.805963) | Angiogenesis and cell adhesion | Neurons and microglia |
rs10793294 | GAB2 | C > A/C > G | C = 0.251454 (A = 0.748546) | Cell proliferation and growth | Oligodendrocytes, microglia, neurons and astrocytes |
rs3745833 | GALP | C > A/C > G/C > T | G = 0.33124 (C = 0.66875) | Neuropeptide | Neurons |
rs6931277 | HLA-DQA1 | A > T | T = 0.14976 (A = 0.85024) | Adaptive immunity | Microglia |
rs1143634 | IL1B | G > A | A = 0.227942 (G = 0.772058) | Inflammatory response | Microglia |
rs35349669 | INPP5D | C > T | T = 0.38287 (C = 0.61713) | Apoptosis, lipid metabolism and immunity | Microglia |
rs10933431 | INPPD5 | G > C | G = 0.30651 (C = 0.69349) | Apoptosis, lipid metabolism and immunity | Microglia |
rs190982 | MEF2C | G > A/G > C | G = 0.376709 (A = 0.623291) | Apoptosis, differentiation, neurogenesis and immune proliferation | Neurons, microglia, oligodendrocytes and astrocytes |
rs190982 | MEF2C | G > A/G > C | G = 0.376709 (A = 0.623291) | Apoptosis, differentiation, neurogenesis and immune proliferation | Neurons, microglia, oligodendrocytes and astrocytes |
rs558678 | MS4A2 | T > G | G = 0.24086 (T = 0.75914) | Immune responses | Neurons |
rs4938933 | MS4A4A | C > G/C > T | C = 0.404463 (T = 0.595537) | Signal transduction and immune responses | Microglia |
rs610932 | MS4A4A | T > C/T > G | T = 0.430441 (G = 0.569559) | Signal transduction and immune responses | Microglia |
rs10897011 | MS4A4E | G > A | A = 0.33764 (G = 0.66236) | Innate immunity | Microglia |
rs610932 | MS4A6A | T > C/T > G | T = 0.430441 (G = 0.569559) | Signal transduction and immune responses | Microglia |
rs7935829 | MS4A6A | A > G | G = 0.35879 (A = 0.64121) | Signal transduction and immune responses | Microglia |
rs2081545 | MS4A6A | C > A/C > T | A = 0.21413 (C = 0.78587) | Signal transduction and immune responses | Microglia |
rs11754661 | MTHFD1L | G > A/G > T | A = 0.061583 (G = 0.938417) | Metabolism | Microglia, neurons, oligodendrocytes and astrocytes |
rs3800324 | PGBD1 | G > A | A = 0.054414 (G = 0.945586) | Unknown | Neurons, oligodendrocytes, astrocytes and microglia |
rs3851179 | PICALM | T > C | T = 0.361052 (C = 0.638948) | Endocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs561655 | PICALM | G > A/G > T | G = 0.348713 (A = 0.651287) | Endocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs541458 | PICALM | C > T | C = 0.315402 (T = 0.684598) | Endocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs10792832 | PICALM | A > C/A > G/A > T | A = 0.29879 (G = 0.70121) | Endocytosis | Oligodendrocytes, microglia, neurons and astrocytes |
rs2058716 | PRKD3 | G > A/G > C | G = 0.31978 (C = 0.68022) | Apoptosis and lipid transport | Microglia, oligodendrocytes, neurons and astrocytes |
rs165932 | PSEN1 | G > A/G > T | G = 0.424510 (T = 0.575490) | Amyloidogenic- and Notch processing | Oligodendrocytes, neurons, microglia and astrocytes |
rs28834970 | PTK2B | T > C | C = 0.31596 (T = 0.68404) | Adaptive immunity | Neurons, microglia, oligodendrocytes and astrocytes |
rs2301275 | PVR | A > C/A > G | G = 0.23252 (A = 0.76748) | Cell adhesion | Neurons, oligodendrocytes, astrocytes and microglia |
rs142787485 | RAB10 | A > G | G = 0.02890 (A = 0.97110) | Protein transport | Oligodendrocytes, neurons, microglia and astrocytes |
rs2376866 | RELB | C > T | T = 0.14727 (C = 0.85273) | Apoptosis, cell growth and immunity | Microglia, neurons, oligodendrocytes and astrocytes |
rs11218343 | SORL1 | T > A/T > C | C = 0.02728 (T = 0.97272) | Endocytosis | Microglia, neurons, astrocytes and oligodendrocytes |
rs2282649 | SORL1 | C > A/C > T | T = 0.28928 (C = 0.71072) | Endocytosis | Microglia, neurons, astrocytes and oligodendrocytes |
rs2306604 | TFAM | A > C/A > G/A > T | G = 0.41883 (A = 0.58117) | Transcription regulation | Oligodendrocytes, neurons, astrocytes and microglia |
rs5011436 | TMEM106B | A > C/A > G/A > T | C = 0.27232 (A = 0.72768) | Lysosomal transport | Neurons, oligodendrocytes, astrocytes and microglia |
rs187370608 | TREM2 | G > A | A = 0.00201 (G = 0.99799) | Phagocytosis and immune activation | Microglia |
rs75932628 | TREM2 | C > A/C > T | T = 0.00232 (C = 0.99768) | Phagocytosis and immune activation | Microglia |
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Kadlecova, M.; Freude, K.; Haukedal, H. Complexity of Sex Differences and Their Impact on Alzheimer’s Disease. Biomedicines 2023, 11, 1261. https://doi.org/10.3390/biomedicines11051261
Kadlecova M, Freude K, Haukedal H. Complexity of Sex Differences and Their Impact on Alzheimer’s Disease. Biomedicines. 2023; 11(5):1261. https://doi.org/10.3390/biomedicines11051261
Chicago/Turabian StyleKadlecova, Marion, Kristine Freude, and Henriette Haukedal. 2023. "Complexity of Sex Differences and Their Impact on Alzheimer’s Disease" Biomedicines 11, no. 5: 1261. https://doi.org/10.3390/biomedicines11051261
APA StyleKadlecova, M., Freude, K., & Haukedal, H. (2023). Complexity of Sex Differences and Their Impact on Alzheimer’s Disease. Biomedicines, 11(5), 1261. https://doi.org/10.3390/biomedicines11051261