PT - JOURNAL ARTICLE AU - Chatila, Zena K. AU - Kim, Eunhee AU - Berlé, Clara AU - Bylykbashi, Enjana AU - Rompala, Alexander AU - Oram, Mary K. AU - Gupta, Drew AU - Kwak, Sang Su AU - Kim, Young Hye AU - Kim, Doo Yeon AU - Choi, Se Hoon AU - Tanzi, Rudolph E. TI - BACE1 Regulates Proliferation and Neuronal Differentiation of Newborn Cells in the Adult Hippocampus in Mice AID - 10.1523/ENEURO.0067-18.2018 DP - 2018 Jul 01 TA - eneuro PG - ENEURO.0067-18.2018 VI - 5 IP - 4 4099 - http://www.eneuro.org/content/5/4/ENEURO.0067-18.2018.short 4100 - http://www.eneuro.org/content/5/4/ENEURO.0067-18.2018.full SO - eNeuro2018 Jul 01; 5 AB - β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ), one of the major pathogenic molecules of Alzheimer’s disease (AD), and is therefore being actively pursued as a drug target for AD. Adult hippocampal neurogenesis (AHN) is a lifelong process that is known to be important for learning and memory and may have the potential to regenerate damaged neural tissue. In this study, we examined whether BACE1 regulates AHN, which holds important implications for its suitability as a drug target in AD. Cohorts of 2-month-old wild-type (BACE1+/+), heterozygous, and homozygous BACE1 knockout mice (BACE1+/– and BACE1–/–, respectively) were injected with 5-bromo-2′-deoxyuridine (BrdU) and sacrificed 1 day later to examine the impact of loss of BACE1 on neural precursor cell (NPC) proliferation in the adult brain. Parallel cohorts of mice were sacrificed 4 weeks after BrdU injection to determine the effects of BACE1 on survival and differentiation of newborn NPCs. We found that NPC proliferation was increased in BACE1–/– mice compared to BACE1+/+ mice, while no difference was observed in NPC survival across genotypes. Differentiation of NPCs to neuronal lineage was impaired in BACE1–/– mice. However, no differences were observed in astrogenesis, the proportion of immature neurons, or the production of oligodendrocytes across genotypes. Importantly, corresponding with a decrease in neuronal differentiation in the absence of a complementary increase in an alternate cell fate, BACE1–/– mice were found to have a pool of undifferentiated NPCs in the hippocampus compared to BACE1+/+ and BACE1+/– mice.