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P1‐184: ESTRADIOL REDUCES BASAL BACE1 EXPRESSION THROUGH THE ACTIVATION OF ESTROGEN RECEPTOR ALPHA
Author(s) -
Marwarha Gurdeep,
Ghribi Othman
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.2018.06.188
Subject(s) - estrogen , estrogen receptor , gper , estrogen receptor alpha , estrogen receptor beta , medicine , endocrinology , fulvestrant , selective estrogen receptor modulator , biology , neuroprotection , chemistry , microbiology and biotechnology , cancer , breast cancer
homogenisation and fractionation of occipital and temporal brain sections. The effects of synthetic monomers and oligomers of amylin were assessed in neurons derived from induced pluripotent stem cells (iPSCs). Western blotting, ELISA and mesoscale analysis were used to measure the effects of amylin on Aß production and degradation and on markers of autophagy. Human occipital grey matter was also used to investigate IAPP (amylin precursor) gene expression by RT-PCR. Results: Immunohistochemistry demonstrated amylin deposits in the vasculature of brain tissue. Investigation of effects of amylin on iPSC derived neurons demonstrated an increase in extracellular Ab levels. Mesoscale assay of levels of sAPPa and sAPPb in media demonstrated no increase in either soluble fragment. This result implies that amylin increases extracellular Aß without influencing cleavage of APP. Our investigation of the potential mechanisms causing increased extracellular Aß suggests amylin may impair autophagy. RT-PCR data demonstrated expression of IAPP gene in human brain fractions and this was upregulated in AD cases. Conclusions: Our results confirm deposition of amylin in cerebral vasculature and provide new data to suggest amylin may be produced by brain tissue. Amylin appears to contribute to AD by increasing cerebral Ab via impairment of autophagy-mediated Aß degradation. The results of this study provide further evidence for amylin as a link between T2D and AD.