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P2‐166: BRANCHED‐CHAIN AMINO ACIDS (BCAAS): A NEW PLAYER IN ALZHEIMER'S DISEASE
Author(s) -
Bakkar Siddik Md Abu,
Moghaddam Masoud Zabet,
Hegde Vijay,
Shin Andrew
Publication year - 2019
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.2019.06.2573
Subject(s) - endocrinology , medicine , insulin resistance , amino acid , type 2 diabetes , biology , metabolism , insulin , diabetes mellitus , biochemistry
hematologic safety of the BBB-penetrating EPO following chronic dosing in AD mice. Methods: 9.5 months old male APPswe PSEN1dE9 transgenic mice were treated with saline (n1⁄411), BBB-penetrable EPO, cTfRMAb-EPO, (3 mg/kg, n1⁄47), or recombinant human EPO (rhu-EPO; 0.6 mg/kg, n1⁄410) 2 days/week subcutaneously for 6 weeks, compared to same-aged C57BL/6 wildtype mice treated with saline (n1⁄410). Six-weeks following treatment initiation, functional memory was assessed with the openfield and Y-maze test, and brains were evaluated for Ab load. Blood was collected at baseline, 4-, 6and 8-weeks for complete blood count and white blood cell (WBC) differential. Results: Chronic treatment with cTfRMAb-EPO caused a significant transient increase in reticulocytes after 4 weeks of treatment without changing any other hematologic parameter. rhu-EPO caused a transient increase in hematocrit, RBC count and hemoglobin at 4-weeks, followed by a significant decrease in all hematologic parameters studied (hematocrit, reticulocytes, red blood cells, mean corpuscular volume and hemoglobin) at 8-weeks following treatment initiation. WBC counts did not differ between any experimental groups. cTfRMAb-EPO caused a significant reduction in brain Ab load and notably, brain Ab(1-42) was significantly higher in the rhu-EPO treated mice compared with cTfRMAb-EPO group. Conclusions: Overall, chronic treatment with cTfRMAb-EPO resulted in better safety and therapeutic indices compared with rhu-EPO, which supports the development of this BBB-penetrating-EPO for AD.