APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

• Published in: Molecular neurodegeneration Vol. 17; no. 1; pp. 62 - 47
• Main Authors: Fernández-Calle, Rosalía, Konings, Sabine C., Frontiñán-Rubio, Javier, García-Revilla, Juan, Camprubí-Ferrer, Lluís, Svensson, Martina, Martinson, Isak, Boza-Serrano, Antonio, Venero, José Luís, Nielsen, Henrietta M., Gouras, Gunnar K., Deierborg, Tomas
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.09.2022; BioMed Central; BMC
• Subjects: Advertising executives; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyotrophic lateral sclerosis; Apolipoprotein E; Apolipoprotein E2 - genetics; Apolipoprotein E3 - genetics; Apolipoprotein E4; Apolipoprotein E4 - genetics; Apolipoproteins; Apolipoproteins E - metabolism; Autophagy; Brain; Cell interactions; Cholesterol; Chromosomes; Clinical Medicine; Clinical trials; Exercise; Gene expression; Genetic aspects; Genomes; Genotype; Genotype & phenotype; Health risk assessment; Humans; Hypotheses; Inflammation; Injuries; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolism; Movement disorders; Multiple sclerosis; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurofibrillary tangles; Neuroinflammation; Neurologi; Neurology; Nucleotides; Parkinson's disease; Pathology; Peptides; Physiology; Plaque, Amyloid - pathology; Proteins; Review; Reviews; Risk factors; Senile plaques; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Structure-function relationships; Tau protein; tau Proteins - genetics; Traumatic brain injury; β-Amyloid; Neuroinflammation; Alzheimer’s disease; Apolipoprotein E; Neurodegeneration
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-022-00566-4

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.