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P1–121: Seladin–1 expression affects APP processing in a cholesterol dependent manner
Author(s) -
Kuehnle Katrin,
Crameri Arames,
Lutjohann Dieter,
Dotti Carlos G.,
Nitsch Roger M.,
Ledesma Maria D.,
Mohajeri Hasan M.
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.2006.05.497
Subject(s) - lipid raft , cholesterol , ectodomain , biology , raft , microbiology and biotechnology , sterol , intracellular , biochemistry , chemistry , receptor , organic chemistry , copolymer , polymer
functions. Histological examinations at this age revealed abundant intraneuronal A aggregates in cortex and hippocampus with no apparent -amyloid plaque load. This early pathology was followed by severe -amyloid angiopathy and plaque formation at later ages. Electrophysiological measurements in hippocampal brain slices of 3 and 7 month old Swe/Arc-APP transgenic mice revealed a severe impairment in long-term potentiation (LTP), with field excitatory postsynaptic potential (fEPSP’s) signals being back to baseline already ten minutes after LTP induction. These data indicate a major functional disturbance of synaptic plasticity correlating with the accumulation of intracellular A aggregates before the onset of bona-fide -amyloid pathology. Conclusion: Together, our in vivo and in vitro data suggest that the formation of intracellular oligomeric or protofibrillar A intermediates can be an early toxic event in the pathophysiological cascade leading to -amyloid formation and neurodegeneration.