| First Author | Belichenko PV | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 3 | Pages | e0152471 |
| PubMed ID | 27023444 | Mgi Jnum | J:253508 |
| Mgi Id | MGI:6092652 | Doi | 10.1371/journal.pone.0152471 |
| Citation | Belichenko PV, et al. (2016) An Anti-beta-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome. PLoS One 11(3):e0152471 |
| abstractText | In Down syndrome (DS) or trisomy of chromosome 21, the beta-amyloid (Abeta) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Abeta as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Abeta is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD). At present, no treatment targets Abeta-related pathogenesis in people with DS. Herein we used a vaccine containing the Abeta 1-15 peptide embedded into liposomes together with the adjuvant monophosphoryl lipid A (MPLA). Ts65Dn mice, a model of DS, were immunized with the anti-Abeta vaccine at 5 months of age and were examined for cognitive measures at 8 months of age. The status of basal forebrain cholinergic neurons and brain levels of APP and its proteolytic products were measured. Immunization of Ts65Dn mice resulted in robust anti-Abeta IgG titers, demonstrating the ability of the vaccine to break self-tolerance. The vaccine-induced antibodies reacted with Abeta without detectable binding to either APP or its C-terminal fragments. Vaccination of Ts65Dn mice resulted in a modest, but non-significant reduction in brain Abeta levels relative to vehicle-treated Ts65Dn mice, resulting in similar levels of Abeta as diploid (2N) mice. Importantly, vaccinated Ts65Dn mice showed resolution of memory deficits in the novel object recognition and contextual fear conditioning tests, as well as reduction of cholinergic neuron atrophy. No treatment adverse effects were observed; vaccine did not result in inflammation, cellular infiltration, or hemorrhage. These data are the first to show that an anti-Abeta immunotherapeutic approach may act to target Abeta-related pathology in a mouse model of DS. |
