title: Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment.
abstract: Adult neurogenesis is modulated by a balance of extrinsic signals and intrinsic responses that maintain production of new granule cells in the hippocampus. Disorders that disrupt the proliferative niche can impair this process, and alterations in adult neurogenesis have been described in human autopsy tissue and transgenic mouse models of Alzheimer's disease. Because exogenous application of aggregated Aβ peptide is neurotoxic in vitro and extracellular Aβ deposits are the main pathological feature recapitulated by mouse models, cell-extrinsic effects of Aβ accumulation were thought to underlie the breakdown of hippocampal neurogenesis observed in Alzheimer's models. We tested this hypothesis using a bigenic mouse in which transgenic expression of APP was restricted to mature projection neurons. These mice allowed us to examine how wild-type neural progenitor cells responded to high levels of Aβ released from neighboring granule neurons. We find that the proliferation, determination, and survival of hippocampal adult-born granule neurons are unaffected in the APP bigenic mice, despite abundant amyloid pathology and robust neuroinflammation. Our findings suggest that Aβ accumulation is insufficient to impair adult hippocampal neurogenesis, and that factors other than amyloid pathology may account for the neurogenic deficits observed in transgenic models with more widespread APP expression.
authors.affiliation: Departments of Neuroscience and Neurology and Neurosurgery, Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yetman
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Jankowsky
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides