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P4–011: Expression of GGA1 is altered in Alzheimer's disease and regulates the generation of amyloid β–peptide
Author(s) -
Wahle Tina,
Sastre Magdalena,
Thal Dietmar R.,
Rentmeister Andrea,
Bogdanovic Nenad,
Famulok Michael,
Heneka Michael T.,
Walter Jochen
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.2006.05.1749
Subject(s) - alpha secretase , amyloid precursor protein secretase , microbiology and biotechnology , amyloid precursor protein , endosome , signal transducing adaptor protein , transmembrane protein , p3 peptide , chemistry , senile plaques , alzheimer's disease , biology , biochemistry , signal transduction , receptor , intracellular , medicine , disease , pathology
elevated at presynaptic areas using an immunoelectron microscopic technique with anti-oligomeric A antibody. Next, the long-term potentiation (LTP) recorded in the dentate gyrus and in the CA1 area of the hippocampus was significantly suppressed in the crossbred mice, compared with APP transgenic mice. The LTP in the dentate gyrus was more strongly suppressed than that in the CA1 area of the hippocampus, reflecting an increase in quantity of A oligomers. Finally, the crossbred mice displayed obvious cognitive abnormalities consistently in different learning and memory paradigms. These results indicate that a reduction in neprilysin activity causes synaptic and cognitive impairment through a local increase of oligomeric A in the synaptic sites of the brain before the onset of amyloid plaque formation. Thus, reduced neprilysin activity appears to be a causative event that is at least partly responsible for the memoryassociated symptoms of AD.