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APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans

Genetic and epidemiological studies have found that variations in the amyloid precursor protein (APP) and the apoliopoprotein E (APOE) genes represent major modifiers of the progressive neurodegeneration in Alzheimer’s disease (AD). An extra copy of or gain-of-function mutations in APP correlate wit...

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Autores principales: Sae-Lee, Wisath, Scott, Luisa L., Brose, Lotti, Encarnacion, Aliyah J., Shi, Ted, Kore, Pragati, Oyibo, Lashaun O., Ye, Congxi, Rozmiarek, Susan K., Pierce, Jonathan T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407474/
https://www.ncbi.nlm.nih.gov/pubmed/32580938
http://dx.doi.org/10.1534/g3.120.401486
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author Sae-Lee, Wisath
Scott, Luisa L.
Brose, Lotti
Encarnacion, Aliyah J.
Shi, Ted
Kore, Pragati
Oyibo, Lashaun O.
Ye, Congxi
Rozmiarek, Susan K.
Pierce, Jonathan T.
author_facet Sae-Lee, Wisath
Scott, Luisa L.
Brose, Lotti
Encarnacion, Aliyah J.
Shi, Ted
Kore, Pragati
Oyibo, Lashaun O.
Ye, Congxi
Rozmiarek, Susan K.
Pierce, Jonathan T.
author_sort Sae-Lee, Wisath
collection PubMed
description Genetic and epidemiological studies have found that variations in the amyloid precursor protein (APP) and the apoliopoprotein E (APOE) genes represent major modifiers of the progressive neurodegeneration in Alzheimer’s disease (AD). An extra copy of or gain-of-function mutations in APP correlate with early onset AD. Compared to the other variants (APOE2 and APOE3), the ε4 allele of APOE (APOE4) hastens and exacerbates early and late onset forms of AD. Convenient in vivo models to study how APP and APOE4 interact at the cellular and molecular level to influence neurodegeneration are lacking. Here, we show that the nematode C. elegans can model important aspects of AD including age-related, patterned neurodegeneration that is exacerbated by APOE4. Specifically, we found that APOE4, but not APOE3, acts with APP to hasten and expand the pattern of cholinergic neurodegeneration caused by APP. Molecular mechanisms underlying how APP and APOE4 synergize to kill some neurons while leaving others unaffected may be uncovered using this convenient worm model of neurodegeneration.
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spelling pubmed-74074742020-08-19 APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans Sae-Lee, Wisath Scott, Luisa L. Brose, Lotti Encarnacion, Aliyah J. Shi, Ted Kore, Pragati Oyibo, Lashaun O. Ye, Congxi Rozmiarek, Susan K. Pierce, Jonathan T. G3 (Bethesda) Investigations Genetic and epidemiological studies have found that variations in the amyloid precursor protein (APP) and the apoliopoprotein E (APOE) genes represent major modifiers of the progressive neurodegeneration in Alzheimer’s disease (AD). An extra copy of or gain-of-function mutations in APP correlate with early onset AD. Compared to the other variants (APOE2 and APOE3), the ε4 allele of APOE (APOE4) hastens and exacerbates early and late onset forms of AD. Convenient in vivo models to study how APP and APOE4 interact at the cellular and molecular level to influence neurodegeneration are lacking. Here, we show that the nematode C. elegans can model important aspects of AD including age-related, patterned neurodegeneration that is exacerbated by APOE4. Specifically, we found that APOE4, but not APOE3, acts with APP to hasten and expand the pattern of cholinergic neurodegeneration caused by APP. Molecular mechanisms underlying how APP and APOE4 synergize to kill some neurons while leaving others unaffected may be uncovered using this convenient worm model of neurodegeneration. Genetics Society of America 2020-06-24 /pmc/articles/PMC7407474/ /pubmed/32580938 http://dx.doi.org/10.1534/g3.120.401486 Text en Copyright © 2020 Sae-Lee et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Sae-Lee, Wisath
Scott, Luisa L.
Brose, Lotti
Encarnacion, Aliyah J.
Shi, Ted
Kore, Pragati
Oyibo, Lashaun O.
Ye, Congxi
Rozmiarek, Susan K.
Pierce, Jonathan T.
APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans
title APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans
title_full APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans
title_fullStr APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans
title_full_unstemmed APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans
title_short APP-Induced Patterned Neurodegeneration Is Exacerbated by APOE4 in Caenorhabditis elegans
title_sort app-induced patterned neurodegeneration is exacerbated by apoe4 in caenorhabditis elegans
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407474/
https://www.ncbi.nlm.nih.gov/pubmed/32580938
http://dx.doi.org/10.1534/g3.120.401486
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