PMID- 11788052
DA - 20020114
DCOM- 20020201
IS - 1044-5498
VI - 20
IP - 11
DP - 2001 Nov
TI - Behavioral assessment of Alzheimer's transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory.
PG - 737-44 AB - Long-term vaccinations with human beta-amyloid peptide 1-42 (Abeta1-42) have recently been shown to prevent or markedly reduce Abeta 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 Abeta deposition at 16 months. In these same mice, Abeta 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 Abeta vaccination, as well as correlational analyses between cognitive performance and Abeta deposition in vaccinated animals. We report that 8 months of Abeta 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" Abeta deposition in both the hippocampus and the frontal cortex of vaccinated APP+PS1 mice. Our results suggest that the behavioral protection of long-term Abeta 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, Abeta vaccination of presymptomatic AD patients could be an effective therapeutic to protect against such cognitive impairments.
AD - The Alzheimer's Research Consortium, Department of Biology, University of
[emd]
FAU - Arendash, G W
AU - Arendash GW
FAU - Gordon, M N
AU - Gordon MN
FAU - Diamond, D M
AU - Diamond DM
FAU - Austin, L A
AU - Austin LA
FAU - Hatcher, J M
AU - Hatcher JM
FAU - Jantzen, P
AU - Jantzen P
FAU - DiCarlo, G
AU - DiCarlo G
FAU - Wilcock, D
AU - Wilcock D
FAU - Morgan, D
AU - Morgan D
LA - eng
ID - AG15490/AG/NIA
ID - AG18478/AG/NIA
PT - Journal Article
CY - United States
TA - DNA Cell Biol
JID - 9004522
RN - 0 (Amyloid beta-Protein)
RN - 0 (Peptide Fragments)
RN - 0 (Vaccines)
RN - 0 (beta-amyloid (1-42))
SB - IM
MH - Alzheimer Disease/immunology/*physiopathology
MH - Amyloid beta-Protein/*administration & dosage/immunology/metabolism
MH - Animal
MH - *Behavior, Animal
MH - Brain/metabolism/pathology
MH - *Memory
MH - Mice
MH - Mice, Transgenic
MH - Peptide Fragments/*administration & dosage/immunology/metabolism
MH - Support, Non-U.S. Gov't
MH - Support, U.S. Gov't, P.H.S.
MH - Vaccines/*administration & dosage
EDAT- 2002/01/15 10:00
MHDA- 2002/02/02 10:01
AID - 10.1089/10445490152717604 [doi]
PST - ppublish
SO - DNA Cell Biol 2001 Nov;20(11):737-44.