Aβ vaccination combined with behavioral enrichment in aged beagles
Thirty-four aged beagles (11-12 years) were assigned, balancing baseline cognitive scores, sex and age, to control, active fibrillar Aβ 1-42 vaccine, behavioral enrichment, or vaccine plus enrichment groups and treated for 20 months. The vaccine (0.5 mg fibrillar Aβ with alum, subcutaneous, boosted at 2 weeks then monthly) reduced brain Aβ and raised CSF Aβ42 and BDNF RNA but increased microhemorrhages, while enrichment reduced brain Aβ and prevented microhemorrhages. The combination produced significant maintenance of learning over time with reduced Aβ and increased BDNF mRNA, but no benefit to memory.
Record
| Design | controlled trial |
|---|---|
| Status | completed |
| Setting | laboratory colony |
| Intervention | Active vaccine against fibrillar Aβ 1-42 (VAC) and behavioral enrichment (ENR), alone and combined |
| Intervention class | combination |
| Comparator | Control/control group: alum-only injections without behavioral enrichment |
| Dose regimen | 0.5 mg fibrillar Aβ with 2% aluminum hydroxide (alum) injected subcutaneously, boosted after 2 weeks and then monthly; control animals received alum injections. Enrichment: two 20-min outdoor group walks weekly, weekly rotation of play toys, and cognitive enrichment tasks |
| Duration | 20 months |
| Dogs | 34 |
| Population note | 34 beagles at study start; groups C/C n=8, C/V n=8, E/C n=8, E/V n=10 |
| Breed | Beagle |
| Age | 11-12 years (abstract); 10.5-13.6 years at study start (full text) |
| Other | 31 dogs from Lovelace Respiratory Research Institute and 3 from Harlan; housed in pairs (n=12) or singly (n=22) in kennels with indoor/outdoor runs |
| Primary outcome | Cognition (learning and memory), brain Aβ and pyroglutamate Aβ, cerebrospinal fluid Aβ42, brain-derived neurotrophic factor mRNA, and microhemorrhages |
| Result (as reported) | 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. |
| Tags | cognition, vaccine, amyloid, enrichment, beagle, brain-aging |
Notes: Groups were assigned by balancing for baseline cognitive test scores, sex and age rather than by stated randomization, so kind is recorded as controlled_trial. Dogs were housed, and procedures approved, at Lovelace Respiratory Research Institute; the full text has no funding statement. Separate from the earlier antioxidant/enrichment longitudinal study, whose kennels and cognitive protocols it reused.
Sources and verbatim quotes
Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages. (2017) PMID 27776266 (results)
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.
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.
Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages. (2017) PMID 27776266 (design)
the longitudinal study started with 34 beagles (10.5 – 13.6 years – Table 1): 31 from Lovelace Respiratory Research Institute (LRRI – Albuquerque, NM) and 3 from Harlan (Riglan Farms, Inc, Mount Horeb, Wisconsin).
Dogs were housed in pairs (n=12) or singly (n=22) in kennel buildings with indoor/outdoor runs measuring 91 cm x 600 cm
each dog received 0.5 mg of fibrillar Aβ (500 μl) that was added to 50 μl of 2% aluminum hydroxide (alum) suspension (Accurate Chemical, Westbury, NY) and 450 μl of PBS and vortexed. All animals that did not receive fibrillar Aβ 1–42 were given alum injections. Animals were immunized subcutaneously in the back of the neck and monitored for adverse reactions. After 2 weeks, animals were boosted with an additional injection followed by monthly injections thereafter.
Dogs in the behavioral enrichment group were given two 20-min walks outdoors in groups of 3–4 animals each week. Play toys were rotated through their kennels on a weekly basis.
Animals were assigned to one of four treatment groups balancing for baseline cognitive test scores, sex, and age. All control animals received alum only as the injection while those receiving the active vaccine were injected with fibrillar Aβ1–42 mixed with alum. These groups included 1) control/control (n=8; C/C); (2) control/vaccine (n=8; C/V); (3) behavioral enrichment/control (n=8; E/C); (4) behavioral enrichment and vaccine (n=10; E/V).
Reproduce: canine_trial_search(trial_id="beagle-abeta-vaccination-behavioral-enrichment") in dog-geroscience-mcp; dataset canine-trial-registry.