Apolipoprotein E intersects with amyloid-β within neurons
(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
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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.
- author
- Konings, Sabine C LU ; Nyberg, Emma LU ; Martinsson, Isak LU ; Torres-Garcia, Laura LU ; Klementieva, Oxana LU ; Guimas Almeida, Claudia and Gouras, Gunnar K LU
- organization
-
- LU Profile Area: Light and Materials
- LTH Profile Area: Nanoscience and Semiconductor Technology
- NanoLund: Centre for Nanoscience
- Medical Microspectroscopy (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Experimental Dementia Research (research group)
- LU Profile Area: Proactive Ageing
- LINXS - Institute of advanced Neutron and X-ray Science
- publishing date
- 2023-08
- 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}}, }