Premium
P1–099: Hyperphosphorylation of tau protein in the brain of a human APP transgenic mouse model
Author(s) -
Rosi Maria Cristina,
Grossi Cristina,
Luccarini Ilaria,
Fiorentini Anna,
Bellucci Arianna,
Casamenti Fiorella
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.2006.05.474
Subject(s) - hippocampus , hyperphosphorylation , dentate gyrus , blot , genetically modified mouse , cortex (anatomy) , neuroscience , immunohistochemistry , hippocampal formation , cerebral cortex , kinase , tau protein , chemistry , transgene , biology , alzheimer's disease , medicine , microbiology and biotechnology , biochemistry , disease , gene
pitulate a number of neuropathological features of the human disorder, including age-dependant abnormal phosphorylation of tau, neurofibrillary tangles and the presence of sarkosyl insoluble PHF-tau in the absence of any disturbance to motor function. Behavioral assessment of tauV337M mice has previously identified age-related memory impairment as indexed by the social transmission of food preferences (STFP) olfactory memory task. We have undertaken further investigations into the cognitive functioning of tauV337M mice, focusing on aspects of attention and impulse control. Deficits in impulse control are among the earliest behavioral changes identified both in humans with the tauV337M mutation and in frontal variant forms of frontotemporal dementia (fvFTD). Evidence of early and pre-symptomatic attentional deficits has also been identified in FTD patients. Using the 5-choice serial reaction time task (5CSRTT), which has been extensively used for assessment of attentional function and impulse control in humans, rats and mice, specific age-related increases in motor impulsivity were identified in tauV337M mice in comparison to littermate wild types. We are currently investigating the neurobiological basis of this impulsivity, and the extent to which it is related to the underlying tau neuropathology. We have used gene expression, pharmacological and neurochemical analyses to identify changes in key neural systems involved in cognition and response inhibition.