APP-Induced Patterned Neurodegeneration Is Exacerbated byAPOE4inCaenorhabditis elegans
| Autor: | Lotti Brose, Jonathan T. Pierce, Pragati Kore, Congxi Ye, Ted Shi, Aliyah J Encarnacion, Susan K Rozmiarek, Lashaun O Oyibo, Wisath Sae-Lee, Luisa L. Scott |
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| Rok vydání: | 2020 |
| Předmět: |
Apolipoprotein E
APOE4 QH426-470 Investigations 03 medical and health sciences 0302 clinical medicine Molecular level mental disorders Genetics Amyloid precursor protein medicine Allele Molecular Biology Gene Genetics (clinical) Caenorhabditis elegans 030304 developmental biology 0303 health sciences biology Neurodegeneration Neuro-degeneration medicine.disease biology.organism_classification C. elegans biology.protein Cholinergic lipids (amino acids peptides and proteins) APP Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | G3: Genes|Genomes|Genetics G3: Genes, Genomes, Genetics, Vol 10, Iss 8, Pp 2851-2861 (2020) |
| ISSN: | 2160-1836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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