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 β-amyloid (Aβ)-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 Aβ 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. JEM © The Rockefeller University Press.