IRS1 and Insulin resistance: Aβ was further shown to potentiate the TNF-α/PICR-dependent activation of PKR, another IRS-1 Ser-kinase in neurons, to drive IRS-1 phosphorylation and insulin resistance as well as ER stress-associated eIF2α induction and subsequent synaptic damage, LTP impairment and memory deficits in vivo.