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P2‐284: Epigenetic mechanisms involving Aβ production in SH‐SY5Y cells treated with anisomycin
Author(s) -
Li Liang
Publication year - 2011
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.2011.05.1162
Subject(s) - anisomycin , sh sy5y , p38 mitogen activated protein kinases , epigenetics , histone , acetylation , microbiology and biotechnology , histone h3 , amyloid precursor protein , biology , kinase , chemistry , protein kinase a , biochemistry , cell culture , medicine , alzheimer's disease , gene , genetics , neuroblastoma , disease
pothesis that oligomeric Ab (oAb) was associated with dementia irrespective of the deposition of insoluble Ab and the formation of NPs. Methods: Postmortem specimens from the superior temporal gyrus (Bm22) of 111 cases ranging in age between 70-102 years with no neuropathology, or only AD-associated neuropathology was studied. Subjects with CDR scores of 0 and 0.5 were designated as non-demented and those with CDR scores > 1 as demented. For Aßx-40 and Aßx-42 ELISAs, antibodies 2G3 and 21F12 were used for capture and 6E10 for detection. For oAb, the 3D6-3D6 capture and detection protocols was used (Arch Neurol 2009;66:190-9).Results:As expected, dementia was associated with higher number of NPs (p < 0.0001) and ELISA measures of soluble and insoluble Ab40 and Ab42, but the dementia-associated rise in these measures diminished to non-significant by age 90 and beyond. In contrast, the levels of oAb were significantly elevated in the dementia groups (p < 0.0001) and remained so (p < 0.05) at virtually all ages. In YO persons all forms of Ab were robustly correlated with the degree of dementia (p< 0.006), in OO persons only the levels of oAb correlated significantly with CDR (r1⁄4 0.46, p< 0.05). Conclusions: Increased levels of brain oAb are central to dementia, even in OO persons when the ability of NPs and levels of soluble and insoluble Ab-40 and Ab-42 to distinguish dementia from non-dementia has become tenuous. These results support the involvement of Ab in dementia and AD pathogenesis, but suggest that in contrast to fibrillar Ab deposits in NPs, increased levels of oAb may be wholly or partially responsible for dementia in both YO and OO persons. oAb is a potentially important target for therapeutic intervention not only in the rapidly expanding population of the OO, but for persons with AD dementia at any age.