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P1‐147: Donepezil Modulates Adam10 and Bace1 Expression in Platelets of Alzheimer's Disease Patients
Author(s) -
Sarno Tamires Alves,
Talib Leda Leme,
Giroud Joaquim Helena Passarelli,
Hototian Sergio,
Gattaz Wagner Farid,
Forlenza Orestes Vicente
Publication year - 2016
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.2016.06.895
Subject(s) - donepezil , adam10 , alzheimer's disease , amyloid precursor protein , medicine , disease , acetylcholinesterase , platelet , dementia , pharmacology , neuroscience , psychology , biology , enzyme , metalloproteinase , biochemistry , matrix metalloproteinase , disintegrin
brain. To investigate this, we are characterising the effects of CD2AP knockdown in an in vitro model of the BBB. Methods: Endogenous CD2AP expression was knocked down in H4 and hMEC/D3 cells using siRNA. Knockdown was quantified by western blot and Image J analysis. Levels of APP, Ab, and APP metabolites were quantified using ELISAs. The rate of receptor-mediated endocytosis was measured by a transferrin uptake assay. Co-localisation of CD2AP with APP and endosomal markers was assessed using immunocytochemistry. Transcytosis in hMEC/D3 cells will be assessed using Transwell assays. Results:We observed a significant 30.2760.07 % increase in Ab40 expression (p1⁄40.0046). Expression levels of APP and APP processing metabolites was not significantly altered. Results from our experiments in progress will be made available at AAIC 2016. Conclusions:Knockdown of CD2AP expression resulted in a significant increase in extracellular amyloid-B (Ab) levels, which did not appear to be directly related to changes in APP processing. This study is ongoing and novel data will be presented at AAIC 2016. Overall, our study provides valuable insights into how CD2AP contributes to LOAD susceptibility.