The Erythrocytic Hypothesis of Brain Energy Crisis in Sporadic Alzheimer Disease: Possible Consequences and Supporting Evidence

Autores de INCLIVA

• 

  Maria Amparo Urios Lluch

  Autor

• 

  María Del Carmen Montoliu Félix

  Autor

Participantes ajenos a INCLIVA

• Kosenko, E
• Tikhonova, L
• Alilova, G

Grupos y Plataformas de I+D+i

• Grupo de Investigación de Deterioro Neurológico

  

  Leading Researcher

  María Del Carmen Montoliu Félix

Abstract

Alzheimer's disease (AD) is a fatal form of dementia of unknown etiology. Although amyloid plaque accumulation in the brain has been the subject of intensive research in disease pathogenesis and anti-amyloid drug development; the continued failures of the clinical trials suggest that amyloids are not a key cause of AD and new approaches to AD investigation and treatment are needed. We propose a new hypothesis of AD development based on metabolic abnormalities in circulating red blood cells (RBCs) that slow down oxygen release from RBCs into brain tissue which in turn leads to hypoxia-induced brain energy crisis; loss of neurons; and progressive atrophy preceding cognitive dysfunction. This review summarizes current evidence for the erythrocytic hypothesis of AD development and provides new insights into the causes of neurodegeneration offering an innovative way to diagnose and treat this systemic disease.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Keywords

• Alzheimer's disease; amyloid beta peptides; brain energy crisis; erythrocytic hypothesis; red blood cells; restoration of energy metabolism