RT Journal Article
SR Electronic
T1 A Two-Year Study with Fibrillar β-Amyloid (Aβ) Immunization in Aged Canines: Effects on Cognitive Function and Brain Aβ
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3555
OP 3566
DO 10.1523/JNEUROSCI.0208-08.2008
VO 28
IS 14
A1 Elizabeth Head
A1 Viorela Pop
A1 Vitaly Vasilevko
A1 MaryAnn Hill
A1 Tommy Saing
A1 Floyd Sarsoza
A1 Michaela Nistor
A1 Lori-Ann Christie
A1 Saskia Milton
A1 Charles Glabe
A1 Edward Barrett
A1 David Cribbs
YR 2008
UL http://www.jneurosci.org/content/28/14/3555.abstract
AB Aged canines (dogs) accumulate human-type β-amyloid (Aβ) in diffuse plaques in the brain with parallel declines in cognitive function. We hypothesized that reducing Aβ in a therapeutic treatment study of aged dogs with preexisting Aβ pathology and cognitive deficits would lead to cognitive improvements. To test this hypothesis, we immunized aged beagles (8.4–12.4 years) with fibrillar Aβ1–42 formulated with aluminum salt (Alum) for 2.4 years (25 vaccinations). Cognitive testing during this time revealed no improvement in measures of learning, spatial attention, or spatial memory. After extended treatment (22 vaccinations), we observed maintenance of prefrontal-dependent reversal learning ability. In the brain, levels of soluble and insoluble Aβ1–40 and Aβ1–42 and the extent of diffuse plaque accumulation was significantly decreased in several cortical regions, with preferential reductions in the prefrontal cortex, which is associated with a maintenance of cognition. However, the amount of soluble oligomers remained unchanged. The extent of prefrontal Aβ was correlated with frontal function and serum anti-Aβ antibody titers. Thus, reducing total Aβ may be of limited therapeutic benefit to recovery of cognitive decline in a higher mammalian model of human brain aging and disease. Immunizing animals before extensive Aβ deposition and cognitive decline to prevent oligomeric or fibrillar Aβ formation may have a greater impact on cognition and also more directly evaluate the role of Aβ on cognition in canines. Alternatively, clearing preexisting Aβ from the brain in a treatment study may be more efficacious for cognition if combined with a second intervention that restores neuron health.