Table 1.

Experimental in vitro and in vivo models for the TDP-43 propagation.

Method	TDP-43 donor cell/source	Recipient cell	TDP-43 propagation/Seeding activity	Reference
In vitro
Conditioned media	CM from HEK293 cells expressing TDP-43	HEK293 cells, primary mouse cortical neuron	O	84
	CM from HEK293 cells treated with ALS insoluble factions	HEK293 cells	X	86
	CM from HEK293 cells expressing wild-type TDP-43 or mutant TDP-43 ΔNLS	HEK293 cells, primary mouse spinal cord cultured cells	X	87
Co-culture system	SH-SY5Y cells harboring phosphorylated TDP-43 aggregates	SH-SY5Y cells	O	85
	HEK293 cells containing pTDP-43 aggregates	HEK293 cells	O	86
	HEK293 cells expressing TDP-43	HEK293 cells	O	84
	SH-SY5Y cells expressing HA-tagged TDP-43	SH-SY5Y cells	O	88
	NSC-34 cells expressing wild-type TDP-43-tdTomato	NSC-34 cells expressing mutant TDP-43 G294A-tGFP	O	89
Using brain lysate or CSF from patients	Insoluble fraction from brain tissue of ALS or FTLD-TDP patient	SH-SY5Y cells	O	85
	ALS patient-derived cerebellum or cortex lysate	Mouse primary cortical neuron	Only in case of treatment of cortex lysate	84
	Insoluble fraction from CNS tissues of ALS patient	HEK293 cells, NSC-34 cells	O	86
	Insoluble fraction from brain tissue of FTLD-TDP patient	HEK293 cells expressed TDP-43	O	90
	CSF-derived ALS or FTD patient	U251 cells	O	91

Method	Material	Model	Symptoms	Reference
In vivo
Intraperitoneal injection	Administration of GW4896 (a chemical inhibitor of exosome biogenesis)	Transgenic mice expressing human TDP-43A315T mutant	Exaggerated abnormal behavioral phenotype	92
Stereotaxic injection	Stereotaxic injection of extracts derived FTLD-TDP patients	Transgenic mice expressing cytoplasmic human TDP-43 (lines CamKIIa-hTDP-43NLSm, rNLS8, and CamKIIa-208)	Time-dependent propagation of TDP-43 pathology	93