Organotypic brain slice cultures to model neurodegenerative proteinopathies

Table 2 BSC studies of tau physiology and pathophysiology

Human Pathology	Slice Culture Pathology	Reference(s)
Phosphorylated / conformationally altered tau	BSCs from 3xTg-AD, JNPL3, Tau_RDΔK and Htau mice all develop increased levels of phosphorylated tau from 1 to 4 weeks in culture. rAAV WT, S320F, P301L/S320F and A152T/P301L/S320F human tau transduced BSCs all accumulate phosphorylated tau by 28 days in vitro (DIV).	[12, 13, 29, 59]
Thioflavin S positive tau inclusions	rAAV P301L/S320F and A152T/P301L/S320F human tau transduced BSCs progressively develop Thioflavin S positive tau inclusions beyond 7 DIV. Tau_RDΔK BSCs accumulate Thioflavin S puncta from 25 DIV.	[29, 59]
Tau-induced cell loss	rAAV A152T/P301L/S320F human tau transduced BSCs develop cell loss by 2 months in culture.	[29]
Tau redistribution	BSCs from 3xTg-AD mice show an accumulation of tau at the membrane by 28 DIV. rAAV P301L/S320F and A152T/P301L/S320F human tau transduced BSCs show somatodendritic accumulation of tau by 28 DIV. Tau_RDΔK BSCs accumulate tau in the somatodendritic compartment.	[13, 29, 59]

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