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Table 2 Summary of studies involving rodent brain-derived tau inoculation

From: Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models

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

  1. NA Not available; PI Post inoculation; AD Alzheimer’s disease; TD Tangle-only dementia, PiD Pick disease, AGD Argyrophilic grain disease, PSP Progressive supranuclear palsy, CBD Corticobasal degeneration; mpffs Mouse preformed fibrils; KI Knock in; KO Knock out; A/P Anterior/posterior; L Lateral; D/V Dorsal/ventral