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Apolipoprotein E intersects with amyloid-β within neurons

Konings, Sabine C LU orcid ; Nyberg, Emma LU ; Martinsson, Isak LU ; Torres-Garcia, Laura LU ; Klementieva, Oxana LU orcid ; Guimas Almeida, Claudia and Gouras, Gunnar K LU orcid (2023) In Life Science Alliance 6(8).
Abstract

Apolipoprotein E4 (ApoE4) is the most important genetic risk factor for Alzheimer's disease (AD). Among the earliest changes in AD is endosomal enlargement in neurons, which was reported as enhanced in ApoE4 carriers. ApoE is thought to be internalized into endosomes of neurons, whereas β-amyloid (Aβ) accumulates within neuronal endosomes early in AD. However, it remains unknown whether ApoE and Aβ intersect intracellularly. We show that internalized astrocytic ApoE localizes mostly to lysosomes in neuroblastoma cells and astrocytes, whereas in neurons, it preferentially localizes to endosomes-autophagosomes of neurites. In AD transgenic neurons, astrocyte-derived ApoE intersects intracellularly with amyloid precursor protein/Aβ.... (More)

Apolipoprotein E4 (ApoE4) is the most important genetic risk factor for Alzheimer's disease (AD). Among the earliest changes in AD is endosomal enlargement in neurons, which was reported as enhanced in ApoE4 carriers. ApoE is thought to be internalized into endosomes of neurons, whereas β-amyloid (Aβ) accumulates within neuronal endosomes early in AD. However, it remains unknown whether ApoE and Aβ intersect intracellularly. We show that internalized astrocytic ApoE localizes mostly to lysosomes in neuroblastoma cells and astrocytes, whereas in neurons, it preferentially localizes to endosomes-autophagosomes of neurites. In AD transgenic neurons, astrocyte-derived ApoE intersects intracellularly with amyloid precursor protein/Aβ. Moreover, ApoE4 increases the levels of endogenous and internalized Aβ
42 in neurons. Taken together, we demonstrate differential localization of ApoE in neurons, astrocytes, and neuron-like cells, and show that internalized ApoE intersects with amyloid precursor protein/Aβ in neurons, which may be of considerable relevance to AD.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Amyloid beta-Protein Precursor/genetics, Apolipoprotein E4/genetics, Apolipoproteins E/genetics, Amyloid beta-Peptides/genetics, Alzheimer Disease/genetics, Neurons/physiology
in
Life Science Alliance
volume
6
issue
8
article number
e202201887
publisher
Rockefeller University Press
external identifiers
  • pmid:37290814
  • scopus:85163907704
ISSN
2575-1077
DOI
10.26508/lsa.202201887
language
English
LU publication?
yes
additional info
© 2023 Konings et al.
id
11707461-ed53-4586-9658-146b6b2c9120
date added to LUP
2023-08-27 22:45:43
date last changed
2024-09-21 16:14:04
@article{11707461-ed53-4586-9658-146b6b2c9120,
  abstract     = {{<p>Apolipoprotein E4 (ApoE4) is the most important genetic risk factor for Alzheimer's disease (AD). Among the earliest changes in AD is endosomal enlargement in neurons, which was reported as enhanced in ApoE4 carriers. ApoE is thought to be internalized into endosomes of neurons, whereas β-amyloid (Aβ) accumulates within neuronal endosomes early in AD. However, it remains unknown whether ApoE and Aβ intersect intracellularly. We show that internalized astrocytic ApoE localizes mostly to lysosomes in neuroblastoma cells and astrocytes, whereas in neurons, it preferentially localizes to endosomes-autophagosomes of neurites. In AD transgenic neurons, astrocyte-derived ApoE intersects intracellularly with amyloid precursor protein/Aβ. Moreover, ApoE4 increases the levels of endogenous and internalized Aβ <br>
 42 in neurons. Taken together, we demonstrate differential localization of ApoE in neurons, astrocytes, and neuron-like cells, and show that internalized ApoE intersects with amyloid precursor protein/Aβ in neurons, which may be of considerable relevance to AD.<br>
 </p>}},
  author       = {{Konings, Sabine C and Nyberg, Emma and Martinsson, Isak and Torres-Garcia, Laura and Klementieva, Oxana and Guimas Almeida, Claudia and Gouras, Gunnar K}},
  issn         = {{2575-1077}},
  keywords     = {{Humans; Amyloid beta-Protein Precursor/genetics; Apolipoprotein E4/genetics; Apolipoproteins E/genetics; Amyloid beta-Peptides/genetics; Alzheimer Disease/genetics; Neurons/physiology}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Life Science Alliance}},
  title        = {{Apolipoprotein E intersects with amyloid-β within neurons}},
  url          = {{http://dx.doi.org/10.26508/lsa.202201887}},
  doi          = {{10.26508/lsa.202201887}},
  volume       = {{6}},
  year         = {{2023}},
}