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P1–384: Association of AD neuropathological hallmarks with biological metals
Author(s) -
Monty Jean-Francois,
Adlard Paul A.,
Volitakis Irene,
Cortes Mikhalina,
Li Qiao-Xin,
Laughton Katrina,
McLean Catriona,
Masters Colin L.,
Cherny Robert,
Villemagne Victor L.,
Bush Ashley I.
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.2006.05.762
Subject(s) - neocortex , zinc , western blot , pathology , chemistry , immunohistochemistry , neurofibrillary tangle , dementia , alzheimer's disease , amyloid (mycology) , biochemistry , biology , neuroscience , medicine , disease , senile plaques , organic chemistry , gene
Cl, I, ClO4 , NO3 , PO4 , SO4 2and heparin, PO4 , SO4 2and heparin showed greater effect during the nucleation phase and early elongation phase compared to the others, and the greatest effect was obtained by SO4 . However, TTR aggregated similarly in the presence of different cations. For L55P TTR, distinct structural features could be observed at different stages of aging, following the order of TTR tetramer, irregular aggregates, protofibrils and mature fibers along the aging process. On the other hand, we found TTR induced increase in intracellular Ca within one minute of application (Ca max 40 6% and pD2 5.3 0.1 M). In addition, studying the intracellular Ca increase by L55P at different stages of ageing indicated that intracellular Ca increase was significantly enhanced by TTR aged for 7 d compared to TTR aged for 0 and 3 d (P 0.01), while intracellular Ca increase was significantly diminished by TTR aged for 14 d (P 0.05). Conclusions: TTR aggregation is mainly mediated by hydrophobic interactions. Anionic interactions are involved in TTR aggregation and proteoglycans might be an important factor in TTR aggregation and extracellular deposition. Disturbance of intracellular Ca is an initial event in TTR-induced cytotoxicity. Protofibrils might be the most cytotoxic species followed by irregular aggregates and TTR tetramers, with mature fibers being the least cytotoxic.