Table 3.
Summary of in vivo tau seeding experiments.
| Model/Seed target | Seed | Injection Site (age) | Results/Significance | References |
|---|---|---|---|---|
| Alz17 (WT 2N4R tau) Tg and nTg mice | Insoluble brain extracts from 6 month old hTauP301S (0N4R P301S tau) Tg mice | Stereotactic hippocampal (3 months) | Hippocampal Gallyus silver staining at 6 months post-injection in Alz17 mice with limited spread thereafter; silver staining limited to the site of injection that did not increase in number or spread in nTg mice | (97) |
| Alz17 (WT 2N4R tau) Tg and nTg mice | Total brain homogenates from AD, TD, PiD, AGD, PSP and CBD; brain lysate from 24 month old APP23 (mutant APP) Tg mice | Stereotactic hippocampal and overlying cerebral cortex (3 months) | Hippocampal Gallyus-Braak silver staining at 6 months post injection near the site of injection in Alz17 mice, and limited pathology at the site of injection at 6 months post-injection for nTg mice; brain lysate from APP23 mice did not induce tau pathology in Alz17 mice 18 months post-injection | (107) |
| hTauP301S (P301S 0N4R tau) Tg mice | Brainstem extracts from ∼5 month old hTauP301S (0N4R P301S tau) mice | Stereotactic hippocampal and overlying cerebral cortex (2 months) | Gallyas silver staining showed pathology near the site of injection as well as in afferent and efferent connected regions | (99) |
| hTauP301S (P301S 0N4R tau) Tg mice | Insoluble brain extracts from 6 month old hTauP301S (0N4R P301S tau) Tg mice | Intraperitoneal injection (3 months) | Increased Gallyas silver staining at 9 months compared to control | (181) |
| tauP301L (P301L 2N4R tau) Tg mice | P301L (K18) fibrils | Stereotactic hippocampal or frontal cortex (3 months) | Injection resulted in phosphorylated and detergent-insoluble tau in the brain, including contralateral to the site of injection; tau aggregation was dose-dependent | (103) |
| JNPL3 (P301L 0N4R tau) Tg mice | WT (K18) fibrils | Stereotactic hippocampal (2 months) or gastrocneumius muscle (IM) or cisterna magna (ICM) | Limited positive tau pathology only in the site of brain injection and connected entorhinal cortex in female but not male mice | (104) |
| THY-Tau22 (G272V/P301S 1N4R tau) Tg and nTg mice | Sarkosyl-insoluble AD brain lysate | Stereotactic hippocampal (3 months) | Limited Gallyas-positive silver pathology staining at the site of injection in nTg and THY-Tau22 Tg mice; Pathology mostly consisted of murine tau | (177) |
| hTauP301S (P301S 0N4R tau) Tg mice | Sucrose gradient fractionated hTauP301S (0N4R P301S) lysate or brainstem extracts | Stereotactic hippocampal and overlying cerebral cortex (2 months) | Total brainstem lysate and some biochemical fractions from the whole brain induced tau pathology at the site of injection and synaptically connected regions at 10 weeks post-injection | (100) |
| T40PL-GFP (P301L 2N4R tau) Tg mice | P301L (2N4R) fibrils (AD-tau seeded) or tau purified from AD brains | Stereotactic hippocampal (2–3 months) | Induced tau pathology at 3 months post-injection | (182) |
| nTg mice | Sarkosyl-insoluble AD-tau, CBD-tau, PSP-tau | Stereotactic hippocampal and overlying cortex (2–3 months) | Induced tau pathology near injection site | (183) |
Highlighted are the mouse models, the type of “seeds” used, the method and timing of seed injection, and the outcome of the experiments. Tg = transgenic; nTg = non-transgenic