D (2001) Behavioral assessment of Alzheimer’s transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory

Long-term vaccinations with human b-amyloid peptide 1-42 (Ab1-42) have recently been shown to prevent or markedly reduce Ab deposition in the PDAPP transgenic model of Alzheimer’s disease (AD). Using a sim-ilar protocol to vaccinate 7.5-month-old APP (Tg2576) and APP1PS1 transgenic mice over an 8-month pe-riod, we previously reported modest reductions in brain Ab deposition at 16 months. In these same mice, Ab vaccinations had no deleterious behavioral effects and, in fact, benefited the mice by providing partial pro-tection 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 ad-ditional behavioral results following long-term Ab vaccination, as well as correlational analyses between cog-nitive performance and Ab deposition in vaccinated animals. We report that 8 months of Ab 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” Ab deposition in both the hippocampus and the frontal cortex of vaccinated APP1PS1 mice. Our results sug-gest that the behavioral protection of long-term Ab vaccinations is task specific, with preservation of hip-pocampal-associated working memory tasks most likely to occur. In view of the early short-term memory deficits exhibited by AD patients, Ab vaccination of presymptomatic AD patients could be an effective ther-apeutic to protect against such cognitive impairments. 73