TABLE 3.
Differences in AD-related biochemical measures in 5xFAD and EFAD mice
| Model | Biochemical Measures | |||||
| <4 Months | 4–8 Months | 8–12 Months | 12–16 Months | ≥16 Months | ||
| 5xFAD | Aβ and apoE solubility | |||||
| Total Aβ | ↑ (♀ > ♂) | ↑↑ (♀ > ♂) | ↑↑↑ (♀ > ♂) | ↑↑↑↑ | ↑↑↑↑↑ | |
| Soluble Aβ42 | ↑ | ↑↑ | ↑↑↑ | n.m. | n.m. | |
| Total apoE | ↑ | ↑↑ | ↑↑↑ | ↑↑↑↑ | n.m. | |
| TBSX-apoE | — | — | n.m. | n.m. | n.m. | |
| APP processing | ||||||
| APP levels | ↑ | ↑↑ | ↑↑↑ | ↑↑↑ | ↑↑↑ | |
| BACE levels | ↑ | ↑↑ | ↑↑↑ | ↑↑↑ | ↑↑↑ | |
| C-terminal fragments | ↑ | ↑↑ | ↑↑↑ | ↑↑↑↑ | ↑↑↑↑ | |
| Neurotrophic factors | ||||||
| BDNF | ↓ | ↓↓ | n.m. | ↓↓↓ | ↓↓↓↓ | |
| pCREB | n.m. | — | ↓ | n.m. | n.m. | |
| Neuroinflammatory cytokines | ||||||
| TNF-α | ↑ | ↑ | ↑↑ | n.m. | n.m. | |
| IL-1β | ↑ | ↑↑ | n.m. | n.m. | n.m. | |
| EFAD | Aβ and apoE solubility | |||||
| Total Aβ | — | ↑ (ε4 > ε3 ≥ ε2) | n.m. | n.m. | n.m. | |
| Soluble Aβ42 | — | ↑ (ε4 > ε3 ≥ ε2; ε4 ♀ > ♂) | n.m. | n.m. | n.m. | |
| Total apoE | n.c. (ε4 < ε3 ≤ ε2) | n.c. (ε4 < ε3 ≤ ε2) | n.m. | n.m. | n.m. | |
| TBSX-apoE | n.c. (ε4 < ε3 ≤ ε2) | n.c. (ε4 < ε3 ≤ ε2) | n.m. | n.m. | n.m. | |
| APP processing | ||||||
| APP levels | n.m. | n.c. (ε4 = ε3 = ε2) | n.m. | n.m. | n.m. | |
| BACE levels | n.m. | n.m. | n.m. | n.m. | n.m. | |
| C-terminal fragments | n.m. | n.m. | n.m. | n.m. | n.m. | |
| Neurotrophic factors | ||||||
| BDNF | ↓ (♀ε4 < ε3 ≤ ε2) | ↓↓ (♀ε4 < ε3 ≤ ε2) | n.m. | n.m. | n.m. | |
| pCREB | ↓ (♀ε4 < ε3 ≤ ε2) | ↓↓ (♀ε4 < ε3 ≤ ε2) | n.m. | n.m. | n.m. | |
| Neuroinflammatory cytokines | ||||||
| TNF-α | n.m. | ↑ (ε4 > ε3) | ↑ (ε4 = ε3) | n.m. | n.m. | |
| IL-1β | n.m. | ↑ (ε4 > ε3) | ↑ (ε4 = ε3) | n.m. | n.m. | |
5xFAD mice: ApoE and Aβ solubility: total Aβ: ELISA (49, 50, 52, 53, 57, 66, 222, 348), soluble Aβ42: in TBS or PBS extraction fraction by ELISA (67, 334, 338, 348), total apoE: ELISA or Western blot (67, 348, 349); TBSX-apoE: in TBSX extraction fraction by ELISA (67). APP processing: APP, BACE, C-terminal fragments by Western blot (49, 52, 53, 58, 67, 222, 329, 336, 337, 339, 348–352). Neurotrophic factors: brain-derived neurotrophic factor (BDNF) and pCREB proteins by Western blot or mRNA by qPCR (55, 61, 336, 350, 352, 353). Neuroinflammatory cytokines: TNF-α, IL-1β by qPCR (185, 329, 342, 351, 354). EFAD mice: ApoE and Aβ solubility: total Aβ: ELISA (66, 172), soluble Aβ42: in TBS extraction fraction by ELISA (66, 73, 172), total apoE: ELISA (66, 70), TBSX-apoE: in TBSX extraction fraction by ELISA (66, 172). APP processing: APP by Western blot (66). Neurotrophic factors: BDNF and pCREB proteins by Western blot (70, 193). Neuroinflammatory cytokines: TNF-α, IL1-β mRNA by qPCR (72, 106). Change: Direction: increase ↑, decrease ↓. Extent: the number of arrows (lower-higher) relative to an earlier age. If known and significant, differences between sex or APOE genotypes are specifically indicated within each cell relative to an earlier age. n.c., no change; n.m., not measured; —, not detectable.