NeuroMolecular Medicine

, Volume 21, Issue 1, pp 12–24 | Cite as

The Promises and Challenges of Erythropoietin for Treatment of Alzheimer’s Disease

  • Jiahong Sun
  • Jan Michelle Martin
  • Victoria Vanderpoel
  • Rachita K. SumbriaEmail author
Review Paper


Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two major challenges for the therapeutic development of EPO for chronic neurodegenerative diseases like AD. The transferrin receptors at the BBB, which are responsible for transporting transferrin-bound iron from the blood into the brain parenchyma, can be used to shuttle therapeutic molecules across the BBB. In this review, we discuss the role of EPO as a potential neurotherapeutic for AD, challenges associated with EPO development for AD, and targeting the BBB transferrin receptor for EPO brain delivery.


Erythropoietin Alzheimer’s disease Transferrin receptor Blood–brain barrier Molecular Trojan horse 



This work was supported by a Grant from The National Institute of Health, NIA R21AG055949 (to RKS).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biopharmaceutical Sciences, School of Pharmacy and Health SciencesKeck Graduate InstituteClaremontUSA
  2. 2.College of MedicineCalifornia Northstate UniversityElk GroveUSA
  3. 3.Department of NeurosciencePomona CollegeClaremontUSA
  4. 4.Department of NeurologyUniversity of CaliforniaIrvineUSA

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