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P1‐191: THE ASTROCYTE AUGMENTS THE PRODUCTION OF AMYLOID‐β OLIGOMERS LEADING TO NEURONAL INJURY
Author(s) -
Jia Jianping,
Wang Wei
Publication year - 2018
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.2018.06.195
Subject(s) - pathogenesis , astrocyte , neuroscience , dementia , amyloid β , apolipoprotein e , alzheimer's disease , amyloid (mycology) , disease , mechanism (biology) , chemistry , biology , microbiology and biotechnology , medicine , pathology , immunology , central nervous system , philosophy , epistemology
Ab42:40 (0.21 vs 0.11, p1⁄4<0.01), Ab38:40 (0.41 vs 0.26, p1⁄4<0.01), Ab42:43(33.15 vs 20.30, p1⁄40.02), and Ab42:38 (0.50 vs 0.42 p1⁄4<0.01). PSEN1 mutations demonstrated significantly increased Ab42:40 and Ab42:38 (w100%, values various) decreased Ab38:40 versus controls (w10%). Ab43:40 was substantially increased in PSEN1 R278I versus controls (0.03 vs <0.01, p1⁄4<0.001). Mass spectrometry identified mutation-specific C-terminal truncation patterns (PSEN1 Y115H: Ab15/16/17:40, PSEN1 int4del: Ab20/37:40, as well as Ab19:40 alongside APP V717I). APP V717I CSF had decreased Ab42:40 and similar Ab42:38 when compared to paired CM from the same donor. Conclusions: Data substantiate two tenants of the tripeptide hypothesis of Ab production: APP V717I mutation favours production of Ab42 and Ab38 over Ab43 and Ab40, and PSEN1 mutations reduce successive proteolytic efficiency without grossly inhibiting g-secretase activity. Ab content of different paired biofluids are not directly comparable, but patterns consistent with the amyloid cascade hypothesis demonstrate the potential of iPSC-derived neuronal models in AD research.