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

Fernández-Calle, Rosalía LU ; Konings, Sabine C LU orcid ; Frontiñán-Rubio, Javier LU ; García-Revilla, Juan LU ; Camprubí-Ferrer, Lluís LU ; Svensson, Martina LU orcid ; Martinson, Isak LU ; Boza-Serrano, Antonio LU ; Venero, José Luís and Nielsen, Henrietta M , et al. (2022) In Molecular Neurodegeneration 17(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer Disease/metabolism, Amyloid beta-Peptides/metabolism, Apolipoprotein E2/genetics, Apolipoprotein E3/genetics, Apolipoprotein E4/genetics, Apolipoproteins E/metabolism, Genotype, Humans, Neurodegenerative Diseases/genetics, Nucleotides, Plaque, Amyloid/pathology, tau Proteins/genetics
in
Molecular Neurodegeneration
volume
17
issue
1
article number
62
publisher
BioMed Central (BMC)
external identifiers
  • pmid:36153580
  • scopus:85138460304
ISSN
1750-1326
DOI
10.1186/s13024-022-00566-4
language
English
LU publication?
yes
id
0e2e95be-599c-4532-8c3f-1105b1e214ee
date added to LUP
2022-10-04 11:02:18
date last changed
2024-06-16 03:38:27
@article{0e2e95be-599c-4532-8c3f-1105b1e214ee,
  abstract     = {{<p>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.</p>}},
  author       = {{Fernández-Calle, Rosalía and Konings, Sabine C and Frontiñán-Rubio, Javier and García-Revilla, Juan and Camprubí-Ferrer, Lluís and Svensson, Martina and Martinson, Isak and Boza-Serrano, Antonio and Venero, José Luís and Nielsen, Henrietta M and Gouras, Gunnar K and Deierborg, Tomas}},
  issn         = {{1750-1326}},
  keywords     = {{Alzheimer Disease/metabolism; Amyloid beta-Peptides/metabolism; Apolipoprotein E2/genetics; Apolipoprotein E3/genetics; Apolipoprotein E4/genetics; Apolipoproteins E/metabolism; Genotype; Humans; Neurodegenerative Diseases/genetics; Nucleotides; Plaque, Amyloid/pathology; tau Proteins/genetics}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Molecular Neurodegeneration}},
  title        = {{APOE in the bullseye of neurodegenerative diseases : impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases}},
  url          = {{http://dx.doi.org/10.1186/s13024-022-00566-4}},
  doi          = {{10.1186/s13024-022-00566-4}},
  volume       = {{17}},
  year         = {{2022}},
}