TY - JOUR
T1 - Apolipoprotein E
T2 - Cholesterol metabolism and Alzheimer's pathology
AU - Pohlkamp, Theresa
N1 - Publisher Copyright:
© 2020 Walter de Gruyter GmbH, Berlin/Boston.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Age is the greatest risk factor for Alzheimer's disease (AD). Today, due to an increase in global life expectancy, AD-related deaths are ranked as the sixth most common cause of death. The allele isoform ϵ4 of apolipoprotein E (ApoE4) is the most important genetic risk factor for AD. Three ApoE isoforms are common in humans: ApoE2, ApoE3, and ApoE4. ApoE3 is the most frequent isoform and considered neutral with regards to AD, whereas the isoform ApoE2 is protective. Thus it is important to understand how ApoE isoforms affect amyloid-β (Aβ) and tau toxicity, the key drivers of AD pathology. Aβ and tau accumulate to form the hallmarks of AD, plaques and neurofibrillary tangles, respectively. ApoE, primarily expressed by astrocytes, is the major lipid transporter in the brain. In this review I summarize some important historic and scientific aspects of our progress in understanding the role of the cholesterol transporter ApoE in the brain, and how the isoform ApoE4 contributes to AD pathology.
AB - Age is the greatest risk factor for Alzheimer's disease (AD). Today, due to an increase in global life expectancy, AD-related deaths are ranked as the sixth most common cause of death. The allele isoform ϵ4 of apolipoprotein E (ApoE4) is the most important genetic risk factor for AD. Three ApoE isoforms are common in humans: ApoE2, ApoE3, and ApoE4. ApoE3 is the most frequent isoform and considered neutral with regards to AD, whereas the isoform ApoE2 is protective. Thus it is important to understand how ApoE isoforms affect amyloid-β (Aβ) and tau toxicity, the key drivers of AD pathology. Aβ and tau accumulate to form the hallmarks of AD, plaques and neurofibrillary tangles, respectively. ApoE, primarily expressed by astrocytes, is the major lipid transporter in the brain. In this review I summarize some important historic and scientific aspects of our progress in understanding the role of the cholesterol transporter ApoE in the brain, and how the isoform ApoE4 contributes to AD pathology.
KW - amyloid-β plaques
KW - apolipoprotein receptor 2/ApoER2/LRP8
KW - endosomal vesicle transport
KW - hyperphosphorylated tau
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U2 - 10.1515/nf-2019-0030
DO - 10.1515/nf-2019-0030
M3 - Review article
AN - SCOPUS:85078213292
SN - 0947-0875
VL - 26
SP - 25
EP - 30
JO - Neuroforum
JF - Neuroforum
IS - 1
ER -