Importantly, inhibition of PKCδ by rottlerin markedly reduces BACE1 expression, Aβ levels, and neuritic plaque formation and rescues cognitive deficits in an APP Swedish mutations K594N/M595L/presenilin-1 with an exon 9 deletion-transgenic AD mouse model.
Here, we confirmed that the increase of miR-34a expression in APP/PS1 mice was earlier than the relevant AD pathological characteristics, such as amyloid-β production, amyloid plaque deposition, and cognitive deficits.
Here, we determined whether dietary D-PUFA would ameliorate Aβ pathology and/or cognitive deficits in a mouse model of AD (amyloid precursor protein/presenilin 1 double mutant transgenic mice).
Our data demonstrates that psen1 splicing interference induces phenotypes that resemble early-stage AD, including cognitive deficit, Aβ<sub>1-42</sub> accumulation and synaptic reduction, reinforcing the potential contribution of zebrafish larvae to studies of human brain diseases.
Chronic LTG treatment rescues the suppressed long-term potentiation, loss of spines and cognitive deficits in AβPP/PS1 mice, known to overexpress a chimeric mouse/human mutant amyloid-β protein precursor (AβPP) and a mutant human presenilin 1 (PS1).
Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages.
Both synaptic and cognitive deficits are reproduced in mice double transgenic for amyloid precursor protein (AA substitution K670N,M671L) and presenilin-1 (AA substitution M146V).