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P1‐246: Alzheimer neuronal degeneration: Extracellular versus intracellular Aß oligomers
Author(s) -
Takamura Ayumi,
Kawarabayashi Takeshi,
Matsubara Tomoko,
Shoji Mikio,
Matsubara Etsuro
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.2010.05.797
Subject(s) - extracellular , intracellular , neurotoxicity , in vivo , mechanism of action , monoclonal antibody , antibody , microbiology and biotechnology , biology , neuroscience , pharmacology , chemistry , toxicity , medicine , immunology , biochemistry , in vitro
age-matched control (n 1⁄4 8) and Alzheimer’s (n1⁄4 18) patients and in transgenic APP mutant mice (J9a) and age-matched wild-type littermate controls (4mo and approx 1yr). Amyloid was detected using immunohistochemical approaches with the antibodies 4G8 and 6F3D. The extent of immunostaining, both intracellular and extracellular, was semi-quantified in white matter using a grading system and differences compared using Mann Whitney. Results: In human post-mortem brain, amyloid was detected in the white matter in both controls and AD cases. However there was significantly more intracellular and extracellular amyloid detected in the white matter in AD brains as compared to controls. There was no evidence of amyloid accumulation in white matter in young wild-type mice and at an older age only weak expression of amyloid was observed in oligodendrocytes. In contrast in young mutant APP mice cellular expression of amyloid was detetected in white matter and this was most marked in older mice in which increased expression of amyloid within oligodendrocytes was observed and marked amyloid deposition. Old APP mutant mice also exhibited white matter pathology, disruption of axonal and myelin integrity. Conclusions: There is marked amyloid accumulation in white matter in AD and mutant mice brains that could contribute to a loss of white matter integrity and functional impairment.