title: Cell therapy: a safe and efficacious therapeutic treatment for Alzheimer's disease in APP+PS1 mice.
abstract: Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2 × Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP + PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Neel R
authors.initials: NR
authors.lastname: Nabar
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Bai
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mayl
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Wang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018782:Maze Learning; D051379:Mice; D008969:Molecular Sequence Data; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D053764:Presenilin-1