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P1–089: Altered navigational strategy use and visuospatial impairments in human amyloid precursor protein transgenic mice
Author(s) -
deIpolyi Amy R.,
Fang Shanna,
Wang Xin,
Mucke Lennart
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.464
Subject(s) - morris water navigation task , neuroscience , genetically modified mouse , psychology , water maze , hippocampal formation , striatum , amyloid precursor protein , transgene , medicine , disease , alzheimer's disease , chemistry , gene , biochemistry , dopamine
we examined whether targeting this fragment specifically would have any therapeutic effect in Tg2576 mice. Methods: Tg2576 transgenic mice were exposed to a chronic dosing regimen: JRF/hAb11/1 antibody or PBS was administered intraperitoneally, once a week, starting at the age of 6 months until 20 months. We measured levels of A 11-40/42 in brain and plasma samples after treatment. The brains were also analyzed histologically for plaque deposition. Behavior tests, such as Y-maze and holeboard, were conducted to monitor cognitive function in these mice. Antibody-amyloid peptide interactions were characterized biophysically by surface plasmon resonance (SPR). Results: After treatment with JRF/hAb11/1, we observed increased plasma levels of both full length and truncated forms of A . Interestingly, mild improvements in cognitive function were observed during times when A levels are known to increase in this mouse model. Conclusions: JRF/hAb11/1 is a novel antibody that demonstrates specificity to the beta-amyloid fragment A 11-40/42. Peripheral administration of this antibody in Tg2576 mice demonstrated a mild improvement in cognitive function during times of active A deposition. In vitro studies suggest that this antibody may be used to monitor progress or development of betaamyloid fibril maturation.