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P1‐138: Characterization of an Alzheimer mouse model over‐expressing mutated human TAU
Author(s) -
Duller Stephan,
Hierzer Michael,
Pammer Tina,
Jungwirth Helmut,
Hutter-Paier Birgit,
Windisch Manfred
Publication year - 2010
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.2010.05.687
Subject(s) - morris water navigation task , genetically modified mouse , tau protein , neuroscience , gene isoform , hippocampus , transgene , tauopathy , human brain , amygdala , biology , neurodegeneration , psychology , alzheimer's disease , pathology , medicine , disease , biochemistry , gene
of AD. Clinico-pathological studies found no or weak correlations between amyloid plaques and dementia; clearance of the deposits did not lead to significant clinical improvement. All recent data have re-allocated attention to non-aggregated A-beta species, the pathogenicity of which is still under scrutinization. Methods: In the present study we made use of the recently engineered APPxPS1-Ki mouse model. Results: We found evidence that these transgenics develop early-onset cognitive impairments, before the spreading of brain amyloidosis. Memory impairments were detected from the age of 3 months under the form of an inability to detect a geometric change in a familiar spatial environment. These impairments testify for an hippocampal dysfunction and mimic some of the symptoms displayed by AD patients. The onset of cognitive disturbances in APPxPS1-Ki mice was paralleled by a large boost in brain soluble and intracellular A-beta content (ELISA on fractionated pools) as it has recently been depicted in AD cases. Also we showed that behavior-evoked neuronal activity was strongly decreased in APPxPS1-Ki mice (quantitative mapping of immediate early genes products) in close relationship with intraneuronal A-beta accumulation. On the other side plaques load did not appear to be a covariate of memory decline. Conclusions: It is concluded that early-onset cognitive deficits in AD are determined by specific A-beta conformations and topographies.