Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages.

Autor: Davis PR; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY, USA., Giannini G; Lovelace Respiratory Research Institute, Albuquerque, NM, USA., Rudolph K; Lovelace Respiratory Research Institute, Albuquerque, NM, USA., Calloway N; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Royer CM; Lovelace Respiratory Research Institute, Albuquerque, NM, USA., Beckett TL; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Murphy MP; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA., Bresch F; Metacog Testing Systems, New Westminster, British Columbia, Canada., Pagani D; dP and Associates, Georgetown, Ontario, Canada., Platt T; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA., Wang X; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Donovan AS; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Sudduth TL; Department of Physiology, University of Kentucky, Lexington, KY, USA., Lou W; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Abner E; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Kryscio R; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Wilcock DM; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Physiology, University of Kentucky, Lexington, KY, USA., Barrett EG; Lovelace Respiratory Research Institute, Albuquerque, NM, USA., Head E; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY, USA. Electronic address: elizabeth.head@uky.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2017 Jan; Vol. 49, pp. 86-99. Date of Electronic Publication: 2016 Sep 26.
DOI: 10.1016/j.neurobiolaging.2016.09.007
Abstrakt: Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer's disease. Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1-42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11-12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); and (4) ENR/VAC (E/V) and treated for 20 months. VAC decreased brain Aβ, pyroglutamate Aβ, increased cerebrospinal fluid Aβ 42 and brain-derived neurotrophic factor RNA levels but also increased microhemorrhages. ENR reduced brain Aβ and prevented microhemorrhages. The combination treatment resulted in a significant maintenance of learning over time, reduced Aβ, and increased brain-derived neurotrophic factor mRNA despite increased microhemorrhages; however, there were no benefits to memory. These results suggest that the combination of immunotherapy with behavioral enrichment leads to cognitive maintenance associated with reduced neuropathology that may benefit people with Alzheimer's disease.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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