APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases
|Fernández Calle, R.
Konings, Sabine C.
Frontinan Rubio, Javier
Garcia Revilla, Juan
Camprubí Ferrer, Lluís
Boza Serrano, Antonio
Venero Recio, José Luis
Nielsen, Henrietta M.
Gouras, Gunnar K.
|Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
|ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the ...
ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell–cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.
|European Union (UE). Marie Curie
Ministerio de Ciencia e Innovación (MICIN). España
Junta de Andalucía
Universidad de Sevilla
|Fernández Calle, R., Konings, S.C., Frontinan Rubio, J., Garcia Revilla, J., Camprubí Ferrer, L., Svensson, M.,...,Deierborg, T. (2022). APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases. Molecular Neurodegeneration, 17 (1), 62. https://doi.org/10.1186/s13024-022-00566-4.