TY - JOUR
T1 - Aβ vaccination in combination with behavioral enrichment in aged beagles
T2 - effects on cognition, Aβ, and microhemorrhages
AU - Davis, Paulina R.
AU - Giannini, Ginevra
AU - Rudolph, Karin
AU - Calloway, Nathaniel
AU - Royer, Christopher M.
AU - Beckett, Tina L.
AU - Murphy, M. Paul
AU - Bresch, Frederick
AU - Pagani, Dieter
AU - Platt, Thomas
AU - Wang, Xiaohong
AU - Donovan, Amy Skinner
AU - Sudduth, Tiffany L.
AU - Lou, Wenjie
AU - Abner, Erin
AU - Kryscio, Richard
AU - Wilcock, Donna M.
AU - Barrett, Edward G.
AU - Head, Elizabeth
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer's disease
KW - Brain
KW - Brain-derived neurotrophic factor
KW - Canine
KW - Cerebrovascular
KW - Dog
KW - Immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=84992409175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992409175&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.09.007
DO - 10.1016/j.neurobiolaging.2016.09.007
M3 - Article
C2 - 27776266
AN - SCOPUS:84992409175
SN - 0197-4580
VL - 49
SP - 86
EP - 99
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -
