Table 1.
Preclinical studies on the effect of systemic inflammation in mouse models for AD.
| Mouse model | Age at first insult | Insult | Stimulus source | Sacrification time after last insult | Effect | Reference |
|---|---|---|---|---|---|---|
| APP/PS1 | 2 and 12 months | 2 µg LPS i.h. | S. abortus equi, Sigma | 7 days | Decreased Aβ deposits; Increased microglial immunoreactivity; Decreased CD45 immunoreactivity. |
(50) |
| 9 months | 0.5 mg/kg LPS i.p. once a week for 13 weeks |
E. coli 0111:B4, Sigma | 4 hours | Decreased Aβ deposits; Increased neuroinflammatory reaction; Elevated lysosomal protease cathepsin Z, APP, APOE, CLU. |
(51) | |
| 3 months | 3 µg i.p. LPS once per week for 12 weeks | E. coli 055:B5, Sigma | Directly after last injection | Increased Aβ deposits. | (46) | |
| 25 months | 4 µg LPS i.h. | S. typhimurium, Sigma | 7 days | Decreased Aβ deposits; Infiltration of BM-derived monocytic cells. |
(52) | |
| 11 or 16 months | 4 µg LPS i.h. | S. abortus equi, Sigma | 7 days | Decreased Aβ deposits; Microglial activation. |
(53) | |
| 11 ± 4 months | 1.5 µg LPS i.p. once per week for 12 weeks | E. coli 055:B5, Sigma | Directly after last injection | Increased Aβ deposits; Microglial activation. |
(45) | |
| 5 and 15 months | 1 mg/kg LPS i.p. | Ultrapure LPS, S. typhimurium, #L6143, Sigma. | 2 and 10 days | Increased Aβ deposits and impairing microglial Aβ clearance; NLRP3 inflammasome activation. |
(40) | |
| 4 and 13–16 months | 0.2 mg/kg LPS i.p. once a day for 2 days |
E. coli O127:B8, #L 3129, Sigma; S. typhimurium, #L 6511, Sigma |
24 hours and 3 months | Decreased neuronal complexity; Impaired long-term potentiation and spatial learning; NLRP3 inflammasome activation. |
(54) | |
| 7 months | 5 mg/kg LPS i.p. | E. coli 055:B5, #L2880, Sigma | 24 hours | Neuronal Apoptosis; Microglial activation; Aggravated cognitive impairment. |
(55) | |
| 4.5 months | 0.1 mg/kg LPS i.v. | E. coli 0111:B4, Sigma | 4 hours | Inflammatory reactions; Sex-specific hippocampal metabolic signatures; Sickness behaviors. |
(56) | |
| APP23 | 3 months | 10 mg/kg LPS i.p. | E. coli 0111:B4, Sigma | 0, 1, 3, and 12 hours | Increased neuroinflammatory reaction; Increased vulnerability of the BBB; Severe sickness behaviors. |
(57) |
| 3 months | 0.5 mg/kg LPS i.p. once or once a day for 4 days | S. typhimurium, Sigma | 5 days, 3, 6, and 9 months | Modified pathological features. | (58) | |
| 3xtg-AD | 3 and 4.5 months | 0.25 mg/kg LPS i.p. twice a week for 4 weeks | E. coli 0111:B4, Sigma. | Directly after last injection | AβPP β-CTP was increased intraneuronal, but Aβ was unchanged. | (59) |
| 4 months | 0.5 mg/kg LPS i.p. twice per week for 6 weeks | E. coli 055:B5, Sigma | 24 hours | No effect on Aβ deposits; Inducing tau hyperphosphorylation. |
(60) | |
| 4 months | 1 mg/kg LPS i.p. |
E. coli
055:B5, Sigma |
6 weeks | long-term impairment on hippocampal neurogenesis and memory. | (61) | |
| 6 months | 0.5mg/kg i.p. twice a week for 6 weeks | E. coli 055:B5, Sigma | 6 weeks | Increased neuroinflammatory reaction; up-regulated γ-secretase; Worsening of behavior; 5-Lipoxygenase pathway affects key neuropathological features. |
(62) | |
| 4 months | 5 mg/kg Poly I:C i.v. | #P9582, Sigma | 11 months | Increased Aβ deposits. | (48) | |
| 5-6 and 11-12 months | Inoculation with 104 tachyzoites of T. gondii or 40 viable eggs of T. muris by o.g. or i.p. once | 5, 7, 9, 35 days | Increased pro-inflammatory response; Increased in immune cell infiltration; Microglial activation. |
(63) | ||
| Tg2576 | 17 months | 10 µg i.h. LPS | S. abortus equi, Sigma | 7 days | Decreased Aβ deposits; Microglial activation. |
(64) |
| 16-17 months | 4 or 10 µg LPS i.h. | S. abortus equi, Sigma | 1, 3, 7, 14, 28 days | Decreased Aβ deposits; Microglial and astrocyte activation. |
(65) | |
| 6 and 16 months | 25 µg LPS i.v. | E. coli 0111:B4, Sigma | 1, 2, 4, 6, 18 hours | Increased Aβ deposits transiently; Inflammatory responses. |
(43) | |
| PDAPP | 2 months | 10 µg LPS i.c.v. daily for two weeks | E. coli 0111:B4, Sigma | Directly after last injection | Increased Aβ deposits; Microglial and astrocyte activation. |
(44) |
| tgSwe | 13 months | 50 μg LPS i.p. | E. coli 055:B5, #L2880, Sigma | 1.5 months | Decreased Aβ deposits; Reduced CD45-immunoreactivity. |
(66) |
| 5xFAD | 3-5 and 13-15 months | 0.01, 0.1, 1, 3 mg/kg LPS i.v. once | E. coli 0111:B4, Sigma | 8 hours | Increased BBB permeability. | (67) |
| 6 and 13 months | 2 µg LPS i.c.v. once or daily | Ultrapure LPS, P. gingivalis, In vivoGen | 7, 14, 28 days | Increased Iba-1 and CD3 positive cells in periventricular area; No effect on Aβ and cognitive impairment. |
(68) | |
| 8 months | Ligature-induced periodontal disease | / | 4 weeks | Decreased plaque-associated microglia; Increased insoluble Aβ42 level. |
(69) | |
| ME7 | 8 and 19 weeks post-inoculation with ME7 | 10 μg LPS i.p. | S. abortus equi, Sigma | 1.5, 3, 6 and 24 hours | Increased levels of IL-1β; Exaggerated sickness behaviors. |
(70) |
| 12, 14 and 15 weeks post-inoculation with ME7 | 0.1 or 0.5 mg/kg of LPS | S. abortus equi, #L5886, Sigma. | 2 hours | Exacerbated neuronal death and sickness behavior. | (71) | |
| 18 weeks post-inoculation with ME7 | 12 mg/kg poly I:C i.p. | Amersham Biosciences | 3, 15 hours | Activated interferon-dependent pro-apoptotic pathways; Heightened acute sickness behaviour and acute neurological impairments. |
(72) | |
| hAPP-J20 | 62 weeks | Inoculation with 109 CFU of live P. gingivalis | / | 5 weeks | Increased Aβ deposits; Trigger neuroinflammation; Enhanced cognitive impairments. |
(73) |
| AppNL-G-F | 20-23 weeks | 1 mg/kg LPS i.p. once a week for 2 weeks | S. abortus equi, #L-5886, Sigma | 2 weeks | Increased Aβ deposits; Increased microgliosis; Reduced clearance of Aβ across blood-CSF barrier; Trigger neuronal dysfunction. |
(47) |
i.h., intrahippocampal; i.p., intraperitoneal; i.c.v., intracerebroventricular; i.v., intravenous.