MAPT and early-onset autosomal dominant Alzheimer disease: Having found that a brain-penetrant, small molecule inhibitor of the ISR, trans-ISRIB,51 prevents Aβ-facilitated LTD and abrogates spatial learning and memory deficits in rats injected with synthetic Aβ,53 we systemically administered ISRIB (2.5 mg/kg, i.p.)24 h prior to i.c.v. injection of Alzheimer’s disease brain tau in middle-aged rats.