Table 4 Studies on cell and animal models demonstrating therapeutic benefit of tau reduction

Tet-repression of Tg-tau expression in rTg4510 mice

Reduced neuronal loss and improved memory function

[282]

hAPP tau−/− crosses

Blocks Aß and excitotoxin mediated neuronal dysfunction

[275]

hAPP (APP23) Dtau or tau−/− crosses

Prevention of Aß-mediated memory deficits and improved survival

[152]

CSF delivered ASOs

Reduces evoked seizures in adult nTg mice

[81]

tau−/− Kcna−/− crosses

Reduced network hyperexcitability in mouse and Drosophila epilepsy models

[141]

Crossing tau−/− mice with nTg mice

Reduces learning and memory deficits due to mild repetitive traumatic brain injury in mice

[57]

Streptozotocin-treated tau−/− and nTg mice

Mitigates cognitive deficits in type-1 diabetes mouse model

[1]

tau−/− Scn1a −/− R1407X loss-of-function truncation mice

Prevents seizure and improves survival in Dravet syndrome mouse model

[112]

shRNA knockdown of Mapt in nTg mouse primary neurons

Prevents Aß-induced axonal transport deficits

[341]

ASO knockdown of Tg-tau overexpression in PS19 mice

Reduced tau pathology, reversal of existing tau pathology. Prevention of neuronal loss. Improved behavioural deficits

[82]

Inducible tau knockdown in APP/PS1 x rTg4510 mice

Prevents tau pathology and neuronal death in presence of Aß pathology

[80]