To investigate whether the neuroprotective effects of BDNF are independent of pathogenic protein accumulation, we used AAVT42 to deliver BDNF cDNA to the hippocampus of three distinct AD mouse models: amyloid precursor protein/presenilin-1 (APP/PS1), which exhibits Aβ pathology; rTg4510, which features phosphorylated-tau (p-tau) and neuronal fibrillary tangles (NTFs); and 3 × Tg, which has both Aβ and p-tau accumulation. Here, MAPT is linked to Alzheimer disease.