Behavioral Assessment of Alzheimer's Transgenic Mice Following Long-Term A� Vaccination: Task Specificity and Correlations between A� Deposition and Spatial Memory

Arendash, Gary W.; Gordon, Marcia N.; Diamond, David M.; Austin, Leigh Ann; Hatcher, Jaime M.; Jantzen, Paul; DiCarlo, Giovanni; Wilcock, Donna; Morgan, Dave
November 2001
DNA & Cell Biology;Nov2001, Vol. 20 Issue 11, p737
Academic Journal
Long-term vaccinations with human �-amyloid peptide 1-42 (A�1-42) have recently been shown to prevent or markedly reduce A� deposition in the PDAPP transgenic model of Alzheimer's disease (AD). Using a similar protocol to vaccinate 7.5-month-old APP (Tg2576) and APP+PS1 transgenic mice over an 8-month period, we previously reported modest reductions in brain A� deposition at 16 months. In these same mice, A� vaccinations had no deleterious behavioral effects and, in fact, benefited the mice by providing partial protection from age-related deficits in spatial working memory in the radial arm water maze task (RAWM) at 15.5 months. By contrast, control-vaccinated transgenic mice exhibited impaired performance throughout the entire RAWM test period at 15.5 months. The present study expands on our initial report by presenting additional behavioral results following long-term A� vaccination, as well as correlational analyses between cognitive performance and A� deposition in vaccinated animals. We report that 8 months of A� vaccinations did not reverse an early-onset balance beam impairment in transgenic mice. Additionally, in Y-maze testing at 16 months, all mice showed comparable spontaneous alternation irrespective of genotype or vaccination status. Strong correlations were nonetheless present between RAWM performance and extent of "compact" A� deposition in both the hippocampus and the frontal cortex of vaccinated APP+PS1 mice. Our results suggest that the behavioral protection of long-term A� vaccinations is task specific, with preservation of hippocampal-associated working memory tasks most likely to occur. In view of the early short-term memory deficits exhibited by AD patients, A� vaccination of presymptomatic AD patients could be an effective therapeutic to protect against such cognitive impairments.


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