Similar to Alzheimer disease [31, 32], the JNK and/or p38K-dependent apoptosis pathway [23] along with increased phosphorylation of Tau (Fig 6C in this study) and p-Thr668 of APP [26], all of which can stimulate neuronal cell death in the hippocampus region, contributing to cognitive and behavioral deficits in HIV-1 Tg rats [36, 37, 81]. Here, APP is linked to early-onset autosomal dominant Alzheimer disease.