G-CSF rescues the memory impairment of animal models of Alzheimer's disease.
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.
Tsai
Kuen-Jer
KJ
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, Republic of China.
Tsai
Yueh-Chiao
YC
Shen
Che-Kun James
CK
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
D016229:Amyloid beta-Peptides; D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine; D000109:Acetylcholine