title: G-CSF rescues the memory impairment of animal models of Alzheimer's disease.
abstract: Most of the current clinical treatments for Alzheimer's disease (AD) are largely symptomatic and can have serious side effects. We have tested the feasibility of using the granulocyte colony-stimulating factor (G-CSF), which is known to mobilize hematopoietic stem cells (HSCs) from the bone marrow into the peripheral blood, as a therapeutic agent for AD. Subcutaneous administration of G-CSF into two different beta-amyloid (Abeta)-induced AD mouse models substantially rescued their cognitive/memory functions. The rescue was accompanied by the accumulation of 5-bromo-2'deoxyuridine-positive HSCs, as well as local neurogenesis surrounding the Abeta aggregates. Furthermore, the level of acetylcholine in the brains of Tg2576 mice was considerably enhanced upon G-CSF treatment. We suggest that G-CSF, a drug already extensively used for treating chemotherapy-induced neutropenia, should be pursued as a novel, noninvasive therapeutic agent for the treatment of AD.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Republic of China.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
authors.forename: Yueh-Chiao
authors.initials: YC
authors.lastname: Tsai
authors.forename: Che-Kun James
authors.initials: CK
authors.lastname: Shen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice
chemical_list: D016229:Amyloid beta-Peptides; D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine; D000109:Acetylcholine