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S2‐02–06: Immunological analysis of Aβ oligomer diversity using conformation‐dependent antibodies
Author(s) -
Glabe Charles
Publication year - 2008
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.2008.05.281
Subject(s) - oligomer , monoclonal antibody , fibril , epitope , antibody , chemistry , amyloid (mycology) , in vitro , antiserum , biochemistry , biology , immunology , inorganic chemistry , organic chemistry
calpain activation with A plaque formation in brains from both AD patients and transgenic (Tg) mice overexpressing amyloid precursor protein (APP). The mice also exhibited axonal termini dynamically misdirected to calpain activation-positive A plaques. Consistently, cerebrospinal fluids from Tg mice and AD patients contained greater quantity of calpain-cleaved spectrin than controls. Genetic deficiency of calpastatin (CS), calpain-specific inhibitor protein, augmented A amyloidosis, tau phosphorylation, microgliosis, somato-dendritic dystrophy and mortality in APP-Tg mice. In contrast, brain-specific CS overexpression resulted in opposite phenotypes. Conclusions: These observations indicate that calpain activation may underlie A -triggered pathological cascade and thus shall become a relevant pharmacological target in the treatment of AD.