Given the well-established interplay between PGC-1α and BDNF in maintaining brain health through exercise (Bi et al., 2024), as well as the significant inhibition of neuronal apoptosis by AAV-PGC-1α infusion in AD brains (Wang et al., 2022a), we propose that PGC-1α might serve as a key regulator in the BDNF-dependent survival of adult hippocampal neurons during AD. Here, PPARGC1A is linked to Alzheimer disease.