Data set for Longitudinal pharmacokinetic and safety studies of an antibody-erythropoietin fusion protein for Alzheimer’s disease.

Erythropoietin (EPO) is a promising Alzheimer's disease (AD) therapeutic but suffers from poor brain penetration, requiring high doses that cause hematopoietic side effects. This study evaluated a transferrin receptor monoclonal antibody-EPO fusion protein (TfRMAb-EPO) designed to enhance brain delivery via receptor-mediated transcytosis. Dose Optimization Study: This study evaluated TfRMAb-EPO pharmacokinetics and effects in C57BL/6J mice through acute and chronic dosing regimens. Acute Study: Single injection with blood collection at 3, 6, and 24h post-dose; euthanasia at 24h.Chronic Study: Weekly dosing (3x/week for 4 weeks, 11 total doses) with blood collection 6h post-injection. Terminal sampling at 3, 6, and 24h after final dose. Washout Study: 4-week treatment (11 doses) followed by 8-week washout period, then final challenge dose with 3, 6, and 24h sampling.Measurements: Plasma AUC0-24 (trapezoid method), hematocrit, metabolic panels, and tissue collection (brain, kidney, liver, spleen) following cardiac perfusion. Organs snap-frozen for subsequent immunoassays.Efficacy Study: APP_SAA KI and APP_WT mice were treated with either TfRMAb-EPO (1 mg/kg 3 days a week SQ) or vehicle for 14 weeks. Measurements: At the end of treatment, nesting, open-field test, and Y maze tests were performed. Brains were harvested and processed for 6E10, Abeta 38, 40, 42, and aggregated abeta.