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Table 4 Summary of studies that involve the inoculation of synthetic in vitro synthesized PFFs

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

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)

  1. NA Not available; PI Post inoculation; T40 Full length tau; X-Tau Cofactor-free self-seeding tau; K18 Truncated tau containg 4 repeats; IAPP Islet amyloid polypeptide; A/P Anterior/posterior; L Lateral; D/V Dorsal/ventral