Immunization reduced Aβ brain deposits in older dogs but did not improve cognition
As they age, dogs, like people, can accumulate beta-amyloid (Aβ) plaques, sticky protein deposits in the brain that are a signature sign of Alzheimer’s disease (AD). In a recent NIA-funded study, immunization prevented these deposits and cleared preexisting ones in older dogs’ brains but yielded only limited cognitive improvement and functional benefit.
Following up on studies in mice that linked immunization and reduced Aβ deposits, researchers studied a similar regimen in 20 8- to 12-year-old beagles. Nine dogs were given 25 injections of fibrillar Aβ1-42 and aluminum salt over a 2-year period (provided to boost the immune response). The control group of 11 dogs received either aluminum salt only or saline only. All of the animals were trained and regularly tested on several learning and memory tasks to assess changes in cognitive function.
The researchers, led by Dr. Elizabeth Head of the University of California, Irvine, found no significant difference in cognition between the immunized dogs and the control groups, as shown by their performance on tasks measuring spatial attention, complex learning, and other aspects of cognition. The only exception was reversal learning, in which positive and negative stimuli are reversed, for which the immunized dogs showed less decline than the control-group dogs.
Overall, there was a significant reduction in Aβ plaques in the immunized dogs’ brains, especially in the prefrontal cortex, seen at the end of the study. Smaller reductions in non-plaque (unassembled) Aβ were observed. Importantly, this unassembled form of Aβ may be most toxic to neurons and their synapses. The authors note that reducing preexisting plaques does not restore neuronal and cognitive function in dogs, as it has in aged mice. The canine results are consistent with vaccine studies in people with AD.