Introduction
Methods
Search strategy
Inclusion criteria
Exclusion criteria
Data extraction and quality assessment
Experimental animal;age at inoculation | Time of termination | Pathological tau (mass; volume) | Brain region of isolation | Application; injection region; coordinates from bregma | Speed of application | Tau pathology | Propagation | References |
---|---|---|---|---|---|---|---|---|
C57BL/6 (endogenous tau); 3 m | 11 m PI | Immunoprecipitated AD-tau oligomers (0.6 µg/site; 2 µl) | NA | Bilateral; Hippocampus (A/P = − 2.06 mm, L = ± 1.75 mm, D/V =− 2.5 mm) | 0.2 µl/min | Inclusion; Th-S positive structures | Hippocampus, frontal cortex, corpus callosum & hypothalamus | [96] |
Immunoprecipitated AD-PHF (0.6 µg/site; 2 µl) | Inclusions | No propagation | ||||||
ALZ17 (2N4R; WT; C57BL/6); 3 m | 6 m, 12 m, & 15 m PI | Brain homogenate from AD (NA; 2.5 µl) | Temporal cortex | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = 1.8 mm); Overlying primary visual cortex; (A/P = -2.5 mm, L = + 2 mm, D/V = 0.8 mm) | 1.25 µl/min | NFT- & NT-like; argyrophilic inclusions | Fimbria, optic tract, medial lemniscus, dorsal thalamus, cerebral peduncle amygdala, thalamus, internal capsule, entorhinal cortex, & fornix | [29] |
Brain homogenate from TD (NA; 2.5 µl) | Hippocampus | NFT- & NT-like; argyrophilic inclusions | ||||||
Brain homogenate from AGD (NA; 2.5 µl) | Amygdala | NFT-like; argyrophilic grains | ||||||
Brain homogenate from CBD (NA; 2.5 µl) | Globus pallidus | NFT-, NT-like, & astrocytic plaques; argyrophilic inclusions | ||||||
Brain homogenate from PSP (NA; 2.5 µl) | Putamen | NFT-, NT-like; argyrophilic inclusion; tufted astrocytes | ||||||
Brain homogenate from PiD (NA; 2.5 µl) | Frontal cortex | NFT-, NT-like; argyrophilic inclusions | No propagation | |||||
PS19 (1N4R; P301S; (C57BL/6 × C3H)F1); 2–5 m | 1 m, 3 m, & 6 m PI | Modified sucrose gradient enriched CBD-tau (0.05 µg; 2.5 µl/site) | Cortical grey matter | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = -2 mm) Overlaying primary visual cortex (A/P = -2.5 mm, L = + 2 mm, D/V = -0.8 mm) | NA | NT-like; oligodendroglial inclusions | CA2, CA3, dentate gyrus, fimbria, subiculum, thalamus, hypothalamus, & mammillary nuclei; no pathology in the overlying cortex | [19] |
Modified sucrose gradient enriched AD-tau (10.5 µg; 2.5 µl/site) | NT-like; inclusions | CA3, lateral septal nuclei, subiculum, white matter tracts with involvement of the fimbria, entorhinal cortex, locus coeruleus, raphe nuclei, supramammillary nuclei, neocortex, & contralateral hemisphere (CA3, entorhinal cortex) | ||||||
Modified sucrose gradient enriched DSAD-tau (12.5 µg; 2.5/ µl) | ||||||||
C57BL/6 (endogenous tau); 2–3 m | 2 d,7 d, 1 m, 3 m, 6 m & 9 m PI | Sarkosyl insoluble AD-tau (4 μg/site; 2.5 μl/site) Sarkosyl insoluble AD-tau (1 μg/site; 2.5 μl) | Frontal cortical gray matter | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = -2.4 mm) Overlying primary visual cortex (A/P = -2.5 mm, L = + 2 mm, D/V = -1.4 mm) | NA | NFT-like; Th-S positive structures | Raphe nucleus, the mamillary area, locus coeruleus, fimbria, corpus callosum & both ipsilateral & contralateral dentate gyrus | [67] |
C57BL/6 (endogenous tau); 15–19 m | 1 m, 3 m, & 6 m | Sarkosyl insoluble AD-tau (1 μg; 2.5 μl) | NP-like; Th-S positive structures | Entorhinal cortex, locus coeruleus, corpus callosum, raphe nucleus, mammillary area & fimbria | ||||
C57BL/6 (endogenous tau); 2–3 m | 1 m, 3 m, 6 m, & 9 m PI | Sarkosyl insoluble AD-tau (2.25 μg/site; 2.5 μl/site) | Frontal cortical gray matter | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V =−2.4 mm) Overlying primary visual cortex (A/P = -2.5 mm, L = + 2 mm, D/V =−1.4 mm) | NA | NFT-like | CA3, dentate gyrus, retrosplenial area, supramammillary nucleus, auditory cortex, & entorhinal cortex | [116] |
Sarkosyl insoluble CBD-tau (1.4 μg/site; 2.5 μl/site) | Frontal cortical gray & white matter | NFT-like; coiled bodies-like; astrocytic plaque-like | CA3, dentate gyrus, ventral hippocampus, fimbria, entorhinal cortex, corpus callosum, mammillary area, dorsal raphe, & olfactory bulb | |||||
Sarkosyl insoluble PSP-tau (2.5 μg; 4 μl) | Frontal cortical gray matter | Unilateral; Thalamus (Dorsal lateral geniculate nucleus) (A/P = -2.5 mm, L = + 2 mm, D/V = -3.4 mm) | NFT-like; astrocytic plaque-like; tufted-astrocyte-like | |||||
THY-Tau22 (1N4R; G272V & P301S; C57BL/6); 3 m | 3 m PI | HMW sarkosyl Insoluble AD-tau (1 μg; 2 μl) | Frontal cortex | Unilateral; Hippocampus (A/P = -2.1 mm, L = + 1.5 mm, D/V = -2.0 mm) | 0.2 µl/min | Inclusions; argyrophilic grains | Ipsilateral CA1, CA3, dentate gyrus, fimbria & corpus callosum | [11] |
C57BL/6 (endogenous tau); 3 m | 3 m & 6 m PI | NT-like; coiled bodies-like; argyrophilic grains-like inclusions | CA1, CA2, the alveus, fimbria, & corpus callosum | |||||
hTau (6 tau isoforms with endogenous tau-KO; C57BL/6); 3 m | 6 m, 9 m, & 11 m PI | Sucrose gradient enriched AD p-tau oligomers (0.12 μg; 2.5 μl) | Cerebral cortex | Bilateral; Hippocampus (A/P = -2.5 mm; L = ± 2.0 mm; D/V = -1.8 mm) | 1.25 µl/min | NFT-like; NT-like | CA2, CA3, dentate gyrus, entorhinal cortex, subiculum, amygdala, corpus callosum, neocortex & septal nuclei | [74] |
T40PL-GFP (2N4R; GFP-tagged P301L-tau; B6C3/F1); 2–3 m | 3 m PI | Sarkosyl insoluble AD-tau (2 μg; 2.5 μl) | NA | Unilateral; (A/P = -2.5 mm, L = + 2 mm; D/V =−2.4 mm) | NA | Inclusions | CA3, dentate gyrus, subiculum, retrosplenial granular cortex, entorhinal cortex, pons, & contralateral/ipsilateral hemisphere | [58] |
C57BL/6 (endogenous tau); 2–3 m | 3 m, 6 m & 9 m PI | Sarkosyl insoluble AD tau (2 µg/site; 5 µl) | Middle frontal gyrus | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2 mm, D/V = − 2.4 mm) Overlaying primary visual cortex (A/P = − 2.5 mm, L = + 2 mm, D/V = − 1.4 mm) | 0.4 µl/min | NFT-like | CA3, dentate gyrus, entorhinal cortex, retrosplenial area, supramammillary nucleus & auditory cortex | [15] |
Sarkosyl insoluble AD tau + Synthetic α-syn mpffs (5 µg/site; 2.5 µl) | ||||||||
α-synKO (endogenous tau & α-syn -/-; C57BL/6); 2–3 m | 3 m, 6 m & 9 m PI | Sarkosyl insoluble AD tau (2 µg/site; 5 µl) | Middle frontal gyrus | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2 mm, D/V = − 2.4 mm) Overlaying primary visual cortex (A/P = − 2.5 mm, L = + 2 mm, D/V = − 1.4 mm) | 0.4 µl/min | NFT-like | CA3, dentate gyrus, entorhinal cortex, retrosplenial cortex, supramammillary nucleus & auditory cortex | |
C57BL/6 (endogenous tau); 10 m | 6 m PI | Sarkosyl insoluble AD- tau (NA; 1.5 µl) | Hippocampus | Unilateral; Hippocampus (A/P = -1.9 mm, L = ± 1.4 mm, D/V = -1.5 mm) | 0.05 µl/min | NT-like; oligodendroglial inclusions | CA1, fimbria, septal nuclei, & periventricular hypothalamus | [45] |
6 m PI | Sarkosyl insoluble AD- tau (NA; 1.2 µl) | Hippocampus | Unilateral; Corpus callosum, (A/P = -1.9 mm, L = ± 1.4 mm, D/V = -1.0 mm) | 0.1 µl/min | NT-like; oligodendroglial inclusions | No propagation | ||
C57BL/6 (endogenous tau); 7 m & 10 m | 4 m & 6 m PI | Sarkosyl soluble AD- tau (NA; 1.2 µl) | Hippocampus | No pathology | No propagation | |||
C57BL/6 (endogenous tau); m, & 10–12 m | 4 m & 6–7 m PI | Sarkosyl insoluble GGT tau (NA; 1.2 µl) | Prefrontal cortex area 8 | NT-like; oligodendroglial inclusions | Ipsilateral & contralateral corpus callosum | |||
C57BL/6 (endogenous tau); 12 m | 6–7 m PI | Sarkosyl insoluble PART tau (NA; 1.2 µl) | Hippocampus | NT-like; oligodendroglial inclusions | Ipsilateral & contralateral corpus callosum | |||
Sarkosyl insoluble ARTAG tau (NA; 1.2 µl) | Temporal white matter | NT-like; astroglial & oligodendroglial inclusions | Ipsilateral & contralateral corpus callosum | |||||
C57BL/6 (endogenous tau); 10–12 m | 6–7 m PI | Sarkosyl insoluble PSP tau (NA; 1.2 µl) | Striatum | Unilateral; Corpus callosum, (A/P = -1.9 mm, L = ± 1.4 mm, D/V = -1.0 mm | 0.1 µl/min | NT-like, & oligodendroglial inclusions | Ipsilateral & contralateral corpus callosum | |
6 m PI | Sarkosyl insoluble PiD tau (NA; 1.2 µl) | Hippocampus | NT-like, & oligodendroglial inclusions | Ipsilateral & contralateral corpus callosum | ||||
Sarkosyl insoluble fFTLD-P301L tau (NA; 1.2 µl) | Hippocampus | NT-like, & oligodendroglial inclusions | Ipsilateral & contralateral corpus callosum | |||||
C57BL/6 (endogenous tau); 12 m | 6–7 m PI | Sarkosyl insoluble GGT (P301T) tau (NA; 1.5 µl) | Frontal cortex | Unilateral; Hippocampus (A/P = -1.9 mm, L = -/ + 1.4 mm, D/V = -1.5 mm) | 0.05 µl/min | NT-like; granular inclusions; coiled body-like | CA1, DG, fimbria, & corpus callosum | [49] |
C57BL/6 (endogenous tau); 7 m | 7 m PI | Sarkosyl insoluble GGT (P301T) tau (NA; 1.5 µl) | Subcortical white matter | Unilateral; Hippocampus (A/P = -1.9 mm, L = -/ + 1.4 mm, D/V = -1.5 mm) | 0.05 µl/min | NT-like; granular inclusions; coiled body-like | CA1, DG, fimbria, & corpus callosum | |
C57BL/6 (endogenous tau); 7 m & 12 m | 4 m & 6–7 m PI | Sarkosyl insoluble GGT (P301T) tau (NA; 1.2 µl) | Frontal cortex | Unilateral; Corpus callosum (A/P = -1.9 mm, L = -/ + 1.4 mm, DV = -1.0 mm) | 0.1 µl/min | NT-like; granular inclusions; coiled body-like | Ipsilateral middle & contralateral corpus callosum | |
C57BL/6 (endogenous tau); 10 m | 5 m PI | Sarkosyl insoluble GGT (P301T) tau (NA; 1.5 µl) | Frontal cortex | Unilateral; Caudate putamen (A/P = 0.14 mm, L = − / + 2, D/V = − 2.5 mm) | 0.05 µl/min | NT-like; granular inclusions; coiled body-like | Restricted | |
C57BL/6 (endogenous tau); 7 m | 4 m PI | Sarkosyl soluble GGT (P301T) tau (NA; 1.5 µl) | Frontal cortex | Unilateral; Hippocampus CA2 (A/P = -1.9 mm, L = -/ + 1.4 mm, D/V = -1.5 mm) | 0.05 µl/min | No pathology | Not applicable | |
C57BL/6 (endogenous tau); 3–4 m | 6–7 m | Sarkosyl insoluble sGGT/fGGT (K317M) tau (NA; 1.5 µl) | Frontal cortex | Unilateral; Hippocampus (A/P = -1.9 mm, L = -/ + 1.4 mm, D/V = -1.5 mm) | 0.05 µl/min | NT-like; granular inclusions; coiled body-like | CA1, DG, fimbria, ipsilateral & contralateral corpus callosum | |
C57BL/6 (endogenous tau); 3–4 m | 6–7 m | Sarkosyl insoluble sGGT/fGGT (K317M) tau (NA; 1.5 µl) | Frontal cortex | Unilateral; Corpus callosum (A/P = -1.9 mm, L = -/ + 1.4 mm, DV = -1.0 mm) | 0.1 µl/min | NT-like; granular inclusions; coiled body-like | CA1, DG, fimbria, ipsilateral & contralateral corpus callosum | |
C57BL/6 (endogenous tau); 3 m & 7 m | 3 m PI | Sarkosyl insoluble AGD-tau with no NFTs (NA; 1.5 µl) | Hippocampus | Unilateral; Hippocampus (A/P = -1.9 mm, L = -1.4 mm, DV = -1.5 mm) | 0.05 µl/min | NT-like; granular inclusions; oligodendroglial inclusions | CA1, fimbria, & ipsilateral corpus callosum | [48] |
C57BL/6 (endogenous tau); 3 m & 12 m | 7 m PI | NT-like; granular inclusions; coiled body-like | CA1, fimbria, ipsilateral & contralateral corpus callosum | |||||
C57BL/6 (endogenous tau); 7 m | 3 m PI | Sarkosyl insoluble PART-tau (NA; 1.5 µl) | NT-like; granular inclusions; coiled body-like | Ipsilateral hippocampus, fimbria, & ipsilateral corpus callosum | ||||
C57BL/6 (endogenous tau); 3 m & 12 m | 7 m PI | NT-like; granular inclusions; coiled body-like | Ipsilateral hippocampus ipsilateral periventricular hypothalamus, septal nuclei, fimbria, ipsilateral, middle & contralateral corpus callosum | |||||
C57BL/6 (endogenous tau); 7 m | 3 m PI | Sarkosyl-soluble PART-tau (NA; 1.5 µl) | No pathology | Not applicable | ||||
Tg601 (2N4R; WT-tau; C57BL/6); 2–3 m | 17–19 m PI | Sarkosyl insoluble AD- tau (2 µg; 2.5 µl) | Frontal cortex | Unilateral; Hippocampus (A/P = -2.5 mm, L = ± 2.0 mm, D/V = -2.0 mm) | 0.25 µl/min | NFT-like; NT-like | Stratum lacunosum-moleculare of CA2, dentate gyrus, fimbria, CA1 pyramidal cell layer, external capsule, & dorsal raphe nucleus | [69] |
Tg30tau (1N4R, P301S and G272V; C57BL/6); 1 m | 5 w PI | Brain homogenate from AD (11 µg; 2 µl) | Frontal cortex | Unilateral; Hippocampus (A/P = -1.8 mm, L = -1.72 mm, D/V = -1.8 mm) | 0.2 µl/min | NFT-like | Ipsilateral & contralateral regions of hippocampus | [4] |
Sarkosyl insoluble AD- tau (1 or 2 µg; 2 µl) | NFT-like | Ipsilateral & contralateral regions of hippocampus | ||||||
hTau (6 tau Isoforms with endogenous tau KO; C57BL/6); 2–3 m | 3 m & 6 m PI | Sarkosyl insoluble FTDP-17 tau with P301L mutation (0.97 ug; 5-6 µl) | Frontal cortex | Unilateral; Hippocampus (A/P = –2.5 mm, L = + 2 mm, D/V = 2.4 mm) | NA | NFT-like; oligodendroglial & astrocytic inclusions | Ipsilateral & contralateral hippocampus, fimbria, corpus callosum, periaqueductal gray | [161] |
Sarkosyl insoluble FTLD-17 tau with E10 + 16 mutation (1 ug; 5-6 µl) | NFT-like, oligodendroglial & astrocytic inclusions | Ipsilateral & contralateral hippocampus, fimbria, corpus callosum, thalamus, hypothalamus, retrosplenial cortex, somatosensory cortex, auditory cortex, & supramammillary nucleus | ||||||
Sarkosyl insoluble FTLD-17 tau with L266V mutation (0.6 ug; 5–6 µl) | NFT-like, oligodendroglial & astrocytic inclusions | Ipsilateral & contralateral hippocampus, fimbria, corpus callosum, thalamus, retrosplenial cortex, somatosensory cortex, & periaqueductal gray | ||||||
C57BL/6 (endogenous tau);–5 days | 1 d, 2 d, 3 d, 1 m, 3 m, & 6 m PI | Sarkosyl insoluble AD- tau (3.84 µg; 1.2 µl) | Frontal cortex | Manually in thalamus | 0.05 µl/min | NT-like, granular inclusions early on; at 3 m inclusions; at the age of 6, no pathology observed | No propagation | [47] |
C57BL/6 (endogenous tau); 3 m | 0 h, 1 d, 2 d, 3 d, 7d, 1 m, 3 m, & 6 m PI | Sarkosyl insoluble AD- tau (5.25 µg; 1.5 µl) | Unilateral; Ventral thalamus (A/P = 1.3 mm, L = − 1.2/ − 1.4 mm, DV = − 3/ − 3.5 mm) | Granules inclusions, NT-like, & p-tau inclusions | Habenula, caudate/putamen, internal capsule, & fimbria | |||
3 m PI | Sarkosyl soluble AD- tau (5.25 µg; 1.5 µl) | No pathology | No propagation | |||||
C57BL/6 (endogenous tau); 1–5 d reinoculated at 3 m | 3 m & 6 m PI | Sarkosyl insoluble AD- tau (3.84 µg; 1.2 µl); reinoculated sarkosyl insoluble AD- tau (5.25 µg; 1.5 µl) | Manually in thalamus; followed by reinoculation Unilateral; Ventral thalamus (A/P = 1.3 mm, L = − 1.2/ − 1.4 mm, DV = − 3/ − 3.5 mm) | Granular inclusions | Caudate/putamen & corpus callosum | |||
C57BL/6 (endogenous tau); 6 m | 3 m PI | Sarkosyl insoluble AD- tau (0.01 µg; 1.5 µl) | Hippocampus | Unilateral; Hippocampus (A/P = − 1.9 mm interaural, L = − 1.4 mm, DV = − 1.8 mm) | 0.05 µl/min | NFT-like & granular inclusions | CA2, dentate gyrus, stratum radiatum, stratum oriens, corpus callosum, fimbria, entorhinal cortex, & cerebral cortex | [7] |
6hTau (6 tau isoforms with endogenous tau-KO; C57BL/6); 6 m | 3 m PI | NFT-, pre-tangles, & granular inclusions | CA2, dentate gyrus, stratum radiatum, stratum oriens, hilius, corpus callosum, fimbria, entorhinal cortex & cerebral cortex | |||||
mtWT (endogenous tau KO; C57BL/6); 3 m | 3 m PI6 m PI | No pathology | Not observed | |||||
C57BL/6 (endogenous tau); 3 m | 6 m PI | Sarkosyl insoluble AD- tau (Brain 1 = 0.5 μgBrain 1, 2, 3, & 3(concentrated) = 1- 4 μg; 2.5 µl/site) | Isocortex | Unilateral; Hippocampus (A/P = − 2.5 mm, L = 2 mm, D/V − 2.4 mm) Overlaying primary visual cortex (A/P = − 2.5 mm, L = 2 mm, D/V − 1.4 mm) | 0.25 µl /min | NFT-like, NT-like | CA2, CA3, DG, fimbria, corpus callosum, retrosplenial area, parietal cortex, somatosensory cortex, entorhinal cortex & similar pattern in contralateral hemisphere | [120] |
htau-AppNL−F/NL−F (6 tau isoforms with endogenous tau KO and mutant APP; C57BL/6) 3 m | Sarkosyl insoluble AD- tau (Brain 1 + 2 = 0.5 μg/site;.5 µl/site) | |||||||
Ptk2b KO; (endogenous tau with Ptk2b -/-; C57BL/6) 3 m | Sarkosyl insoluble AD- tau (Brain 1 + 2 = 0.5 μg/site; 2.5 µl/site) | |||||||
Tmem106b KO (endogenous tau with Tmem106b -/-; C57BL/6) 19 m | Sarkosyl insoluble AD- tau (Brain 1 + 2 = 0.5 μg/site; 2.5 µl/site) | |||||||
Grn KO; (endogenous tau with Grn -/-; C57BL/6) 3 m | Sarkosyl insoluble AD- tau (Brain 1 + 2 = 0.5 μg/site; 2.5 µl/site) | |||||||
SHR72 (2N4R, truncated tau aa151–391; SHR) 2 m | 4 m PI | Sarkosyl insoluble AD- tau (600 ng; NA) | Parietal cortex | Bilaterally; Hippocampus (A/P = − 3.6 mm, L = ± 2.0 mm, D/V = − 2.3 mm) | 1.25 μl/min | NFT-like; argyrophilic inclusions | Rostral and caudal to site of injection in CA1 | [140] |
2 m PI | Sarkosyl insoluble AD- tau from 3 independent brains (600 ng; NA) | Unilaterally; Hippocampus (A/P = − 3.6 mm, L = ± 2.0 mm, D/V = − 2.3 mm) | Contralateral hippocampus | |||||
4 m PI | Solubilised sarkosyl insoluble AD- tau (600 ng; NA) | Bilaterally; Hippocampus (A/P = − 3.6 mm, L = ± 2.0 mm, D/V = − 2.3 mm) | No pathology | Not applicable | ||||
4 m PI | Sarkosyl insoluble AD- tau (400/600 ng; NA) | Unilaterally; Hippocampus (A/P = − 3.6 mm, L = ± 2.0 mm, D/V = − 2.3 mm) | NFT-like; argyrophilic tau inclusions | Contralateral hippocampus | ||||
P301ST43 (1N4R; P301S; C57BL/6) 3 m | 4 m PI | AD CSF tau (1 ng; 5 μl) | CSF | Unilateral; Hippocampus (A/P = − 2.5 mm, L = − 2.0 mm, D/V = − 1.8 mm) | 1.25 μl/min | NFT-like & dot-like inclusions | Ipsilateral CA2, CA3, dentate gyrus, & contralateral hippocampus | [138] |
6hTau (6 tau isoforms with endogenous tau-KO; C57BL/6) 3–5 m | 1, 3 & 6 m PI | Sarkosyl insoluble AD-tau (1 µg/site; NA) | Frontal cortex | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2 mm, D/V = − 2.4 mm) Overlaying primary visual cortex (A/P = − 2.5 mm, L = + 2 mm, D/V = − 1.4 mm) | NA | NT-like, NFT-like inclusions; argyrophilic inclusions | Ipsi- & contralateral CA1, CA2, dentate gyrus, subiculum, motor cortex, entorhinal cortex, visual cortex, thalamus, hypothalamus, corpus collosum | [71] |
Sarkosyl insoluble PiD-tau (1 µg/site; NA) | NFT-like; oligodendroglial inclusions; argyrophilic inclusions | Ipsi- & contralateral CA1, CA2, dentate gyrus, fimbria, thalamus, entorhinal cortex, visual cortex | ||||||
Sarkosyl insoluble CBD-tau (1 µg/site; NA) | NFT-like; NT-like; argyrophilic inclusions; astrocytic & oligodendroglial inclusions | Ipsi- & contralateral CA1, CA2, dentate gyrus, fimbria, subiculum, thalamus, hypothalamus, corpus collosum, entorhinal cortex, visual cortex | ||||||
Sarkosyl insoluble PSP-tau (1 µg/site; NA) | NFT-like; argyrophilic inclusions; astrocytic & oligodendroglial inclusions | Ipsi- & contralateral CA1, CA2, dentate gyrus, fimbria, corpus collosum, thalamus, hypothalamus, entorhinal cortex, visual cortex | ||||||
T44mTauKO (0N3R human tau; endogenous tau KO); 3–5 m | 1, 3 & 6 m PI | Sarkosyl insoluble AD-tau (1 µg/site; NA) | Frontal cortex | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2 mm, D/V = − 2.4 mm) Overlaying primary visual cortex (A/P = − 2.5 mm, L = + 2 mm, D/V = − 1.4 mm) | NA | No pathology | NA | |
Sarkosyl insoluble PiD-tau (1 µg/site; NA) | NFT-like; oligodendroglial inclusions | NA | ||||||
Sarkosyl insoluble CBD-tau (1 µg/site; NA) | No pathology | NA | ||||||
Sarkosyl insoluble PSP-tau (1 µg/site; NA) | No pathology | NA | ||||||
TauKDncre;fl/fl (Neuron specific tau KO; C57BL/6); 2–3 m | 1,3,6 & 9 m PI | Sarkosyl insoluble PSP-tau (1 µg/site; NA) | Frontal cortex | Unilateral; Hippocampus (A/P = − 2.5 mm; L = + 2.0 mm; D/V = -2.4 mm) Overlaying primary visual cortex (A/P = − 2.5 mm; L = + 2.0 mm; D/V = -1.4 mm) | NA | No pathology | Not applicable | [115] |
Sarkosyl insoluble CBD-tau (1 µg/site; NA) | Astrocytic plaque-like; coiled body-like | Ipsi- & contralateral CA2, CA3, dentate gyrus, fimbriae, corpus callosum, visual cortex | ||||||
Sarkosyl insoluble PSP-tau (1 µg/site; NA) | Tufted astrocytes; coiled body-like | |||||||
Tau.P301L (2N4R; P301L-tau; C57BL/6) 3 m | 7 d and 28 d PI | Sarkosyl insoluble AD-tau (NA; 2 µl) | Frontal cortex | Unilateral; Hippocampus (A/P = − 1.83 mm; L = + 1.29 mm; D/V = + 1.7 mm) | 0.25 µl/min | NFT-like | Hippocampal formation, cortex, corpus callosum, alveus of ipsi- & contralateral hemisphere | [38] |
hTau (6 tau isoforms with endogenous tau-KO; C57BL/6); 3 m | 1 & 12 m PI | Brain homogenate from CBD; (8 μg; 2 μl) | Frontal cortex | Unilateral; Right Striatum (A/P = 0.8 mm posterior, L = 1.95 mm, D/V = 3.0 mm) | 0.2 μl/30 s | NT-like; astrocytic plaque-like; coiled body-like | Ipsi- & contralateral entorhinal striatum, contralateral striatum, corpus collosum | [171] |
LRRK2G2019S mice (Endogenous tau; LRRK2 KI; C57BL/6); 3–4 m | 1, 3, 6, & 9 m PI | Sarkosyl insoluble AD-tau; (1 μg/site; 2.5 μl/site) | Frontal/temporal cortex | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2.0 mm, D/V = 2.4) Overlying cortex (A/P = -2.5 mm, L = + 2.0 mm, D/V = 1.4 mm) | 0.4 μl/min | NFT-like; NT-like | CA2, CA3, entorhinal cortex, dentate gyrus, ventral tegmental area, ipsilateral supramammillary nucleus, ipsilateral perirhinal area, medial septal nucleus, parasubiculum, presubiculum, pontine reticular nucleus, & ipsilateral accessory olfactory bulb | [32] |
hTau (6 tau isoforms with endogenous tau KO; C57BL/6); 9–11 m | 2.5 m PI | Sarkosyl insoluble AD-tau; (0.55 µg; 2.0 µl) | Isocortex | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2.0 mm, D/V = − 1.67 mm) | 1.25 µl/min | Inclusions | Ipsi- & contralateral regions of hippocampus | [109] |
PS19 (1N4R; P301S; C57BL/6) 3 m | 3 m PI | Sarkosyl insoluble AD-tau; (1 µg; 2.0 µl) | Frontal cortex | Bilateral; Hippocampus (A/P = − 2.4 mm, L = + 1.5 mm, D/V = − 1.6 mm) | 0.2 µl/min | NFT-like; NT-like | CA2, CA3, overlaying isocortex | [106] |
HMW tau 2.33 µl/site | NFT-like; NT-like | CA2, CA3, overlaying isocortex, peri-/entorhinal |
Experimental animal; age at inoculation | Time of termination | Rodent derived brain inoculum (pathological tau);(mass; volume) | Application; injection region (coordinates from bregma) | Speed of application | Pathology | Propagation | References |
---|---|---|---|---|---|---|---|
ALZ17 (2N4R; WT; C57BL/6); 3 m | 6 m PI | Brain homogenate from P301ST43 (1N4R, P301S-tau); (NA; 2.5 µl) | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = -1.8 mm) Overlaying primary visual cortex; (A/P = -2.5 mm, L = + 2 mm, D/V = 0.8 mm) | 1.25 µl/min | NFT-like; NT- like; coiled bodies; argyrophilic inclusions | Fimbria, thalamus, hippocampus, optical tract, medial lemniscus, zona incerta, cerebral peduncle, visual cortex, hypothalamus, superior colliculus, & substantia nigra | [30] |
12 m | Fimbria, thalamus, internal capsule, caudate putamen, somatosensory cortex, hippocampus, optical tract, medial lemniscus, zona incerta, cerebral peduncle, visual cortex, hypothalamus, amygdala, superior colliculus, substantia nigra, entorhinal cortex, & deep mesencephalic nucleus | ||||||
15 m PI | Fimbria, thalamus, internal capsule, caudate putamen, somatosensory cortex, hypothalamus, amygdala, hippocampus, optical tract, medial lemniscus, zona incerta, cerebral peduncle, visual cortex, superior colliculus, substantia nigra, entorhinal cortex, deep mesencephalic nucleus, & pontine nuclei | ||||||
SHR72 (0N4R; truncated tau, aa151–391); 2 m | 25 d & 3.5- 5 m PI | Sarkosyl insoluble from SHR24 (0N3R, truncated tau aa151–391); (0.1 µg; 2 µl) | Unilateral; Motor cortex 1; (A/P = + 3 mm, L = + 2 mm, D/V = − 0.75 mm) | 0.5 µl/min | NFT-like | Ipsilateral frontal cortical areas & striatum | [100] |
SHR24 (0N3R, truncated tau, aa151–391); 2 m | Sarkosyl insoluble tau from SHR72 (0N4R tau, aa151–391); (0.04 µg; 2 µl) | Unilateral; Motor cortex 1; (A/P = + 3 mm, L = + 2 mm, D/V = − 0.75 mm) | NFT-like | Ipsilateral frontal cortical areas, contralateral frontal cortex, & striatum | |||
P301ST43 (1N4R; P301S; C57BL/6) 2 m, 2.5 m, 3 m, 4 m, & 4.5 m | 1 d, 14 d, 1 m, 2 m, & 2.5 m PI | Sarkosyl insoluble tau from P301ST43 (1N4R, P301S-tau); (0.04 ng; 2.5 µl) | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = -1.8 mm) Overlying primary visual cortex; (A/P = − 2.5 mm, L = + 2 mm, D/V = − 0.8 mm) | 1.25 µl/min | NFT-like; NT-like; argyrophilic inclusions | CA3, dentate gyrus, contralateral hippocampus, subiculum & retrosplenial cortex, mammillary nucleus, supramammillary nucleus, thalamus, nucleus accumbens, & lateral septal nucleus | [1] |
rTg4510 (2N4R; P301L; C57BL/6); 2–3 m | 2 d & 21 d PI | Brain extract from rTg4510 (0N4R, P301L-tau, HMW); (0.25 µg; 2.5 µl) | Unilateral; Hippocampus (A/P =−2.5 mm, L = 2.0 mm, D/V =−1.8 mm) | 0.2 µl/min | NFT like inclusions | CA2, CA3, & dentate gyrus | [146] |
Sarkosyl insoluble tau from rTg4510 (0N4R, P301L-tau, LMW); (0.25 µg; 2.5 µl) | No pathology | No spreading | |||||
P301ST43 (1N4R; P301S; C57BL/6); 2.5 m | 2.5 m PI | Total brainstem lysates from P301ST43 (1N4R, P301S-tau); (NA; 2.5 μl) | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2.0 mm, D/V = 1.8 mm) Overlaying primary visual cortex; (A/P = − 2.5 mm, L = + 2 mm, D/V = − 0.8 mm) | 1.25 µl/min | NFT-like; NT-like | Ipsi- & contralateral CA2, dentate gyrus, subiculum, thalamus, mammillary nuclei & retrosplenial cortex | [80] |
40% sucrose gradient fraction from P301ST43 (1N4R, P301S-tau); (NA; 2.5 μl) | NFT-like; NT-like | Ipsi- & contralateral CA2, CA3, dentate gyrus, subiculum, thalamus, mammillary nuclei & retrosplenial cortex | |||||
10% fractions gradient fractions from P301ST43 (1N4R, P301S-tau); (NA; 2.5 μl) | NFT-like (low in numbers) | Ipsi- & contralateral CA2, CA3, dentate gyrus, & subiculum |
Experimental animal; age at inoculation | Time of termination | EVs source (pathological tau);(mass; volume) | Application; injection region (coordinates from bregma) | Speed of application | Pathology | Propagation | References |
---|---|---|---|---|---|---|---|
C57BL/6 mice; 3-4 m | 1 m & 2 m PI | Exosomes derived from neuronally-differentiated, human iPSCs contain human tau-RD-LM-YFP; 2.5 µg | Unilateral; Hippocampus (A/P = -2.0 mm, L = + 1.5 mm, D/V = -1.3 mm) | 0.5 µl/min | NFT-like | Ipsilateral thalamic nuclear regions (TH), piriform/entorhinal (Pir/EC) cortices and contralateral CA1 | [163] |
C57BL/6); 2 m | 5w PI | Exosomes derived from neuronally-differentiated, human iPSCs from fAD patient harbouring an A246E mutation to PS1; 1.34 µg | Bilateral; Hippocampus (A/P = -2.0 mm, L = ± 1.75 mm, D/V = -1.75 mm) | NA | Inclusions | No propagation | [12] |
ALZ17 mice (2N4R; WT; C57BL/6); 3 m | 6 m PI | 4-6 m old WT mice; 2.5 µg | Bilateral; Hippocampus CA1 (A/P = -2.5 mm, L = ± 2 mm, D/V = -1.8 mm) | 0.25 µl/min | No pathology | NA | [13] |
6 m PI | 4-6 m old rTg4510 mice; 2.5 µg | Oligomeric tau inclusions | Stratum radiatum, Schaffer collateral fibers from the CA3 to CA1 region | ||||
C57BL/6 mice; 18-19 m | 4.5 m PI | Human AD brain (frontal cortex) derived EVs; 0.0003 µg | Unilateral; Hippocampus DG (A/P = -2.18 mm, L = ± 1.13 mm, D/V = -1.9 mm) | NA | Inclusions | Both ipsilateral and contralateral hippocampal region including the CA1, CA3, dentate granule cells, subgranular zone, and hilus | [131] |
Human prodromal AD brain (frontal cortex) derived EVs; 0.0003 µg | |||||||
THY-tau30; 1 m | 1 m PI | AD BD-EVs 2 mL; 6 × 109 vesicle | Bilateral; Hippocampus DG (A/P = − 2.5 mm, L = ± 1 mm, D/V = − 1.8 mm) | 0.2 mL/min | NFT-like | CA1 | [99] |
PSP BD-EVs 2 mL; 6 × 109 vesicle | No pathology | NA | |||||
PiD BD-EVs 2 mL; 6 × 109 vesicle | No pathology | NA |
Study characteristics
Results
Deep insight into the tau inoculum
In vivo recapitulation of the tau pathology
Selective regional vulnerability of tau propagation
Experimental animal; age at inoculation | Time of termination | Pathological tau (mass; volume) | Application; injection region (coordinates from bregma) | Speed of application | Pathology | Propagation | References |
---|---|---|---|---|---|---|---|
C57BL/6; 2–3 m | 3,6,9, 18, & 24 m PI | Heparin-treated 2N4R tau PFFs (9 µg; 5 µl) | Unilateral; Hippocampus (A/P = -2.54 mm, L = + 2 mm, D/V = -2.4 mm) Overlaying primary visual cortex (A/P = -2.54 mm, L = + 2 mm, D/V = -1.4 mm) | NA | No pathology | Not applicable | [67] |
Self-aggregated 2N4R tau PFFs (9 µg; 5 µl) | Inclusions | Ipsilateral entorhinal cortex, mammillary area, & contralateral hippocampus | |||||
PS19 (1N4R; P301S; C57BL/6); 2–3 m | 1, 3, 6 m PI | Heparin-treated Myc tagged K18 (4R)/P301L tau PFFs (5 µg; 5 µl) | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = -1.8 mm) Unilateral; Striatum (A/P = + 0.2 mm, L = + 2 mm, D/V = -2.6 mm) Overlaying primary visual cortex (A/P = + 0.2 mm, L = + 2 mm, D/V = − 0.8 mm) | NA | Inclusions | Substantia nigra, thalamus, locus coeruleus, dorsal raphe nuclei, & neocortex | [75] |
Heparin-treated Myc tagged 4R2N/P301S tau PFFs (10 µg; 5 µl) | CA2, dentate gyrus, entorhinal cortex, locus coeruleus, substantia nigra, striatum, thalamus, & corpus callosum | ||||||
P301L (2N4R; P301L-tau; C57BL/6); 3 m | 2, 7, 14 d 1,2 & 3 m PI | Heparin-treated Myc K18 (4R)/P301L tau PFFs (0.05–25 μg; 2–5 µl) | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = − 2.4 mm) | 1 µl/min | NFT-like; Th-S positive structures & argyrophilic inclusions | CA3, dentate gyrus, piriform cortex, & hippocampus | [123] |
Unilateral; Frontal cortex area 3; (A/P = + 2 mm, L = + 2 mm, D/V = − 2.7 mm) | Amygdala, thalamus, midbrain, & brainstem | ||||||
T40PL-GFP (2N4R; GFP tagged P301L; B6C3H/J); 2–3 m | 3 m PI | Heparin-treated Alexa Fluor 594-tagged 2N4R/P301L tau PFFs (2 μg; 2.5 μl) | Unilateral; Hippocampus (A/P = -2.5 mm, L = + 2 mm, D/V = 2.4 mm) | NA | NFT-like | Ipsi- & contralateral CA3, dentate gyrus, subiculum, & retrosplenial granular cortex | [58] |
rtg4510 (2N4R P301L; C57BL/6 X FVB); 28 d | 1 m & 2.5 PI | Heparin-treated hTau (2N4R) short filaments (SFs) (5 μg; 2.5 μl) | Unilateral; Cerebral motor cortex 1 (A/P = − 2.5 mm, M/L = 2 mm, D/V = 1 mm) | 0.5 μl/min | Inclusions | No propagation | [164] |
PS19 (1N4R; P301S; C57BL/6); 2.5 m | 5 m PI | Heparin-treated K18 (4R) tau PFFs (3 µg; 3 µl) | Unilateral; Hippocampus (A/P = − 2.2, L = − 1.6, D/V = − 1.2) | 0.3 µl/ min | NT-like | Ipsi- & contralateral hippocampus & cerebral cortex | [162] |
PS19 (1N4R; P301S; C57BL/6); 3 m | 1 & 3 m PI | Heparin-treated His tagged K18 (4R) tau PFFs (5 μg; 5 μl) | Unilateral; Hippocampus (AP = − 2.5 mm, L = − 2.0 mm, DV = − 1.8 mm) | 0.2 μl/min | Inclusions | Ipsi- & contralateral hippocampus, ipsilateral dentate gyrus, entorhinal cortex, retrosplenial cortex | [173] |
Heparin-treated IAPP-K18 (4R) tau PFFs (5 μg; 5 μl) | |||||||
P301L (2N4R, P301L; C57BL/6); 4 m | 6 w PI | Heparin-treated His-tagged K18 (4R)/P301L tau PFFs (5 µg; 1 µl) | Unilateral; Hippocampus (A/P = -1.8 mm, L = -1.72 mm, D/V = -1.8 mm) | 0.2 µl/min | NFT-like | Ipsi- & contralateral hippocampus | [4] |
PS19 (1N4R; P301S; C57BL/6); 2–3 m | 14 d, 1,3, 6 & 12 m PI | Heparin-treated Myc tagged 2N4R/P301S tau PFFs (4 µg; 1 µl) | Unilateral; Locus Coeruleus (A/P = − 5.45 mm, L = + 1.28 mm, D/V = − 3.65 mm) | 0.1 µl/min | NFT- & NT-like | Ipsilateral locus coeruleus, nucleus prepositus hypoglossi, nucleus paragigantocellularis, hypothalamus, amygdala, bed nucleus of the stria terminali, frontal cortex, & spinal cord | [76] |
PS19 (1N4R; P301S; C57BL/6); 3 m | 1.5, 3.5, 6 and 12 m PI | Heparin-treated K18(4R)/P301L tau PFFs (333 μM; 5 µl | Unilateral; Hippocampus (A/P = -2.0 mm, L = + 1.4 mm, D/V = -1.2 mm) Overlying frontal Cortex (A/P = + 2.0 mm, L = + 1.4 mm, D/V = − 1.0 mm) | 1 µl/min | NFT-like | Ipsi- & contralateral hippocampus & frontal cortex | [144] |
Entorhinal cortex (A/P = − 4.8 mm, L = − 3.0 mm, D/V = − 3.7 mm) | Subiculum, hippocampal formation, amygdala, thalamus & frontal cortex | ||||||
Substantia Negra (A/P = − 4.8 mm, angle 16, L = − 1.1 mm, D/V = − 4.7 mm) | Striatum, thalamus, brain stem & cortical regions including the motor cortex | ||||||
PS19 (1N4R; P301S; C57BL/6); 4 m | 3 m PI | Heparin-treated K18(4R)/P301L tau PFFs (66.7 µM; NA) | Unilateral; Hippocampus (A/P = − 2.0 mm, L = + 1.4 mm, D/V = − 1.4 mm) Overlying frontal cortex (A/P = + 2.0 mm, L = + 1.4 mm, D/V = − 1.0 mm) | 1 µl/min | NFT-like | Ipsi- & contralateral hippocampus & frontal cortex | [155] |
Aβ-induced K18(4R)/P301L tau PFFs (66.7 µM; NA) |
Experimental animal; age at inoculation | Time of termination | Pathological tau (mass; volume) | Brain region of isolation | Application; injection region (coordinates from bregma) | Speed of application | Pathology | Propagation | Modulation | References |
---|---|---|---|---|---|---|---|---|---|
SHR72 (2N4R, truncated tau aa151–391; SHR); 2 m | 4 m PI | Sarkosyl insoluble AD-tau (0.6 & 0.9 µg; 1.5 µl/site) | Parietal cortex | Bilateral; Hippocampus (A/P = − 3.6 mm; L = + / − 2.0 mm; D/V = 3.3 mm) | 1.25 μl/min | NFT-like | Ipsilateral CA1, CA2, CA3 | Enriched environment reduced tau pathology | [107] |
P301S (1N4R; P301S tau; C57BL/6); 4–4.5 m | 2 m PI | Sarkosyl insoluble AD-tau (0.3 µg; 3 µl) | Cerebral cortex | Unilateral; Hippocampus (A/P = -2.5, L = + 2 mm, D/V = -1.8 mm) | NA | NFT-like | Ipsi- & contralateral hippocampus | Chronic intermittent hypoxia enhanced tau pathology | [86] |
PS19 (1N4R; P301S; C57BL/6); 3 m | 2 m PI | Myc tagged K18(4R)/P301L tau PFFs (333 μM; 5 μl) | Synthetic | Unilateral; Frontal cortex (A/P = + 2.0 mm, L = + 1.4 mm, D/V = − 1.0 mm) | 1 μl/min | NFT-like | Cortex | Inhibition NLRP3–ASC or knock out for ASC reduced tau propagation | [142] |
PS19 (1N4R; P301S; C57BL/6); 3 m + MCC950 (Inhibitor of NLRP3–ASC) | |||||||||
PS19 ASC (1N4R; P301S & ASC + / + ; C57BL/6); 3 m | |||||||||
PS19 ASC KO (1N4R; P301S & ASC -/-; C57BL/6); 3 m | |||||||||
PS19 (1N4R; P301S-tau; C57BL/6); 3.5 m | 4.5 m PI | K18(4R)/P301L tauu PFFs (333 μM; 5 μl) | Synthetic | Unilateral; Hippocampus (A/P =−2.0 mm, L = + 1.4 mm, D/V =−1.4 mm) Frontal cortex (A/P = + 2.0 mm, L = + 1.4 mm, D/V =−1.0 mm) | 1 μl/min | Inclusions | Ipsilateral hippocampus & frontal cortex | Absence of NLRP3 led to reduction in tau propagation | [143] |
PS19 NLRP3 KO (1N4R; P301S-tau & NLRP3 -/-; C57BL/6); 3.5 m | |||||||||
PS19 NLRP3 (1N4R; P301S-tau & NLRP3 + / + ; C57BL/6); 3.5 m | |||||||||
PS19 (1N4R; P301S; C57BL/6); 3 m PS19 (1N4R; P301S; C57BL/6); 3 m + colony-stimulating factor 1 receptor inhibitor (PLX5622) PS19, Ikbkb inactivation (1N4R; P301S; Ikbkb -/-, C57BL/6); 3 m PS19, Ikbkb activation (1N4R; P301S; Cx3cr1 CreERT2/ + ; IkbkbCAF/F), 3 m | 1 m PI | Brain homogenates from PSP (12.9 μg; 3 μl) | NA | Unilateral; Hippocampus (A/P = − 2.5 mm, L = + 2 mm, D/V = − 1.8 mm) | NA | Inclusions | Ipsilateral hippocampus & cortex Ipsilateral hippocampus & cortex Ipsilateral cortex Ipsilateral hippocampus | Removal of microglia or inactivation of NF-kB reduced tau propagation in the cortex, activation of NF-kB increase tau propagation in the hippocampus | [159] |
K18 P301L tau (5 μg; 2 μl) | Synthetic | ||||||||
K18 P301L tau) (0.4 μg; 2 μl) | |||||||||
PS19 (1N4R; P301S; C57BL/6); | 2 m PI | rTg4510 brain homogenates (NA; 2 μL) | NA | Unilateral; Hippocampus (A/P = − 2.5 mm, L = − 2 mm, D/V = − 1.8 mm) | NA | NFT-like | Ipsi- & contralateral hippocampus | Absence of Atg7 enhanced tau pathology | [167] |
PS19 Atg7 KO (1N4R; P301S Atg7fl/fl and Cx3cr1CreER; C57BL/6); 2–3 m | |||||||||
5xFAD/PS19 (1N4R; P301S; C57BL/6);4 m | 3 m PI | Heparin-treated K18(4R)/P301L tau PFFs (333 µM; 5µL) | Synthetic | Unilateral; Hippocampus (A/P = − 2.0 mm, L = + 1.4 mm, D/V = − 1.4 mm) Overlying frontal cortex (A/P = + 2.0 mm, L = + 1.4 mm, D/V = − 1.0 mm) | 1 µl/min | NFT-like | Ipsi- & contralateral hippocampus & frontal cortex | Depletion of microglia attenuates Aβ‑facilitated tau pathology and neurodegeneration | [103] |