From: The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ
Cytokinesa | Animals | Main AD-like Pathology and initiating time | Cytokines Expression System | Expression Duration | Resultsb | Ref. | ||
---|---|---|---|---|---|---|---|---|
Delivery Method | Administration Routes | Immuno-histochemistry | Behaviors | |||||
IL-1β | 3xTg AD mice (9 months old) | Aβ plaque: 6 mo. Tau: 12 -15 mo. | anti-IL-1R blocking antibody | Peritoneal Injection | every 8-9 days for 6 months | Aβ deposition ↓; Tau phosphorylation ↓ | Cognition ↑ | [83] |
Rats adult | - | IL-1β injections | Cerebral ventricles | 1 d | TNF-α, IL-10 ↑ | No significance | [34] | |
8 d | TNF-α, IL-1β ↑ IL-10 ↓; APP mRNA ↑ | Memory ↓ | ||||||
3xTg AD mice (8 months old) | Aβ plaque: 6 mo. Tau:12 -15 mo. | IL-1β-XAT cassette | Subiculum | 1 and 3 mo. | Aβ deposition ↓; Tau phosphorylation ↑ | \ | [41] | |
APPswe/PSEN1dE9 mice (8 months old) | Aβ plaque: 6 mo. | rAAV2-IL-1β | Hippocampi | 1 mo. | Aβ deposition ↓ | \ | [42] | |
IL-6 | TgCRND8 mice (0 -12 h old (P0)/36 -48 h old (P2)) | Early Aβ plaque: 3mo. Dense-cored plaques: 5 mo. | rAAV2/1-IL-6 | Cerebral ventricles | 5 mo. | Aβ deposition ↓ | \ | [46] |
TgCRND8 mice (4 mo.) | rAAV2/1-IL-6 | Hippocampi | 1-1.5 mo. | Aβ deposition ↓ | \ | |||
Tg2576 mice (P0) | Numerous Aβ plaques:11-13 mo. | rAAV2/1-IL-6 | Hippocampi | 3 mo. | Aβ deposition ↓ | \ | ||
IL-4 | Tg2576 + PS1 mice (3 months old) | Aβ plaques: 6 mo. | rAAV2/1-IL-4 | Hippocampi | 5 mo. | Aβ↓; Gliosis ↓; Neurogenesis ↑ | Spatial learning ↑ | [54] |
TgCRND8 mice (4 months old) | Early Aβ plaque: 3 mo. | rAAV2/1-IL-4 | Hippocampi | 1.5 mo. | Aβ↑; Gliosis ↑ | \ | [55] | |
APPswe/PSEN1dE9 mice (3 months old) | Aβ plaque: 6 mo. | rAAV2/1-IL-4 | Frontal cortex, Hippocampi | 43 d. | Aβ↓ with no significance; Enhanced M2a phenotype of microglia | \ | [56] | |
IL-10 | APPswe/PSEN1dE9 mice (3 months old) | Aβ plaques: 6 mo. | rAAV2/1-IL-10 | Hippocampi | 5 mo. | Aβ =; Gliosis ↓; Neurogenesis ↑. | Spatial learning ↑ | [52] |
TgCRND8 mice (P0/P2) | Early Aβ plaque: 3mo. | rAAV2/1-IL-10 | Cerebral ventricles | 6 mo. | Aβ deposition ↑ | Cognition ↓ | [51] | |
Tg2576 mice (8 months old) | Numerous Aβ plaques: 11-13 mo. | rAAV2/1-IL-10 | Hippocampi | 5 mo. | Aβ deposition ↑ | Cognition ↓ | ||
APPswe/PSEN1dE9 mice | Aβ plaque: 6 mo. | Bred with IL-10 KO mice | The whole body | 12-13 mo. | Aβ deposition ↓ | Cognition ↑ | [53] | |
IL-12/IL-23 | APPswe/PSEN1dE9 mice | Aβ plaque: 6 mo. | Bred with p40 (IL-12 and IL-23 shared) KO, p35 (IL-12) KO or p19 (IL-23) KO mice | The whole body | 4 mo. | Aβ deposition ↓ (especially with p40 KO) | Cognition ↑ | [65] |
Senescence accelerated mouse (SAMP8) mice (6 months old) | Accelerated aging. | siRNA KO of p40 | Dorsal third ventricle | 1 mo. | Aβ deposition ↓ | Cognition ↑ | [66] | |
TNF-α | TgCRND8 mice (4 months old) | Early Aβ plaque: 3 mo. | rAAV2/1-TNF-α | Hippocampi | 1.5 mo. | Aβ deposition ↓ | \ | [40] |
3xTg AD mice (10, 17 months old) | Aβ plaque: 6 mo. Tau: 12 -15 mo. | TNF-α-lowering agent (3,6'-dithiothalidomide) | Peritoneal Injection | 1.5 mo. | APP, Aβ peptide and Aβ deposition ↓; Tau phosphorylation ↓ | Cognition ↑ | [37] | |
3xTg AD mice (6 months old) | TNF-α-lowering agent (IDT) | Oral administration | 10 mo. | Fibrillar Aβ↓; PHF-tau ↓ | Cognition ↑ | [39] | ||
TGF-β | hAPP J9 line mice | Aβ plaques :5-7 mo. | Bred with transgenic expressing astrocytes-induced TGF-β1 mice | Brain | 12-15 mo. | Aβ deposition ↓; Perivascular Aβ deposition ↑ | \ | [57] |
Transgenic mice with inducible neuron-specific expression of TGF-β1 (3 months old) | - | The heterologous tTA system | Neocortex, hippocampi, striatum | 54 d | Perivascular Aβ deposition ↑ | \ | [62] | |
24 d | Death of neurons induced by 3-nitropropionic acid ↓ | \ | ||||||
SD rats with Aβ1-42 injection in bilateral hippocampus | Aβ | TGF-β1 injection 7 d after Aβ injection | Left cerebral ventricles | 3d | APP ↓ | Cognition ↑ | [166] | |
SD rats with Aβ1-42 injection in bilateral hippocampus | Aβ | TGF-β1 administration1h prior to Aβ injection | Cerebral ventricles | 7 d | APP ↓; PP2A ↑; TNF-α, IL-1β, iNOS, IFN-γ, IL-2, IL-17 and IL-22 ↓. | Cognition ↑ | [58] | |
TGF-β1 administration7 d after Aβ injection | Nares | 7 d | PP2A ↑; IL-1β, iNOS, IFN-γ, IL-2 and IL-17 ↓. | Cognition ↑ | ||||
IFN-γ | APP Tg J20 mice | Aβ plaques : 5-7 mo. | Bred with Tg SJL mice expressing IFN-γ | The whole body | 9 mo. | Oligodendrogenesis ↓ | \ | [167] |
3xTg AD mice (2 months old) | Aβ plaque: 6 mo. Tau:12 -15 mo. | rAAV2/1- IFN-γ | Hippocampi | 10 mo. | Aβ deposition ↑; Tau phosphorylation ↓ | \ | [168] | |
TgCRND8 mice P2 | Early Aβ plaque: 3mo. Dense-cored plaques: 5 mo. | rAAV2/1- IFN-γ | Cerebral ventricles | 5 mo. | Aβ deposition ↓; Gliosis ↑; Complement expression ↑; Peripheral monocytes infiltration ↑ | \ | [63] | |
TgCRND8 mice (4 months old) | Hippocampi | 1.5 mo. | ||||||
JNPL3 mice (P2), rTg4510 mice (P2) | Tau:4 mo. | rAAV2/1- IFN-γ | Cerebral ventricles | 3 mo. | Soluble tau phosphorylation ↑ | \ | [87] |