title: Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-β-associated neuropathology in Alzheimer mice.
abstract: Alzheimer's disease (AD) is the most common progressive age-related dementia in the elderly and the fourth major cause of disability and mortality in that population. The disease is pathologically characterized by deposition of β-amyloid plaques neurofibrillary tangles in the brain. Current strategies for the treatment of AD are symptomatic only. As such, they are less than efficacious in terms of significantly slowing or halting the underlying pathophysiological progression of the disease. Modulation by cell therapy may be new promising disease-modifying therapy. Recently, we showed reduction in amyloid-β (Aβ) levels/β-amyloid plaques and associated astrocytosis following low-dose infusions of mononuclear human umbilical cord blood cells (HUCBCs). Our current study extended our previous findings by examining cognition via (1) the rotarod test, (2) a 2-day version of the radial-arm water maze test, and (3) a subsequent observation in an open pool platform test to characterize the effects of monthly peripheral HUCBC infusion (1×10(6) cells/μL) into the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) from 6 to 12 months of age. We show that HUCBC therapy correlates with decreased (1) cognitive impairment, (2) Aβ levels/β-amyloid plaques, (3) amyloidogenic APP processing, and (4) reactive microgliosis after a treatment of 6 or 10 months. As such, this report lays the groundwork for an HUCBC therapy as potentially novel alternative to oppose AD at the disease-modifying level.
authors: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, Florida 33613, USA.
authors: Donna
authors: D
authors: Darlington
authors: Juan
authors: J
authors: Deng
authors: Brian
authors: B
authors: Giunta
authors: Huayan
authors: H
authors: Hou
authors: Cyndy D
authors: CD
authors: Sanberg
authors: Nicole
authors: N
authors: Kuzmin-Nichols
authors: Hua-Dong
authors: HD
authors: Zhou
authors: Takashi
authors: T
authors: Mori
authors: Jared
authors: J
authors: Ehrhart
authors: Paul R
authors: PR
authors: Sanberg
authors: Jun
authors: J
authors: Tan
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000523:psychology / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D003071:Cognition; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008570:Memory, Short-Term; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009048:Motor Skills; D058225:Plaque, Amyloid / Q000473:pathology / Q000628:therapy; D020127:Recovery of Function; D045442:Rotarod Performance Test
chemical_list: D016564:Amyloid beta-Protein Precursor; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse