Papers by Aliyah Jushe Encarnacion
G3: Genes, Genomes, Genetics, Aug 1, 2020
Genetic and epidemiological studies have found that variations in the amyloid precursor protein (... more 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 e4 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.
Archives of Physical Medicine and Rehabilitation
Genetic and epidemiological studies have found that variations in the amyloid precursor protein (... more 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 or gain-of-function mutations inAPPlower age of AD onset. Compared to the other isoforms (APOE3andAPOE2), the ε4 allele ofAPOE(APOE4) hastens and exacerbates early and late onset forms of AD. Convenientin vivomodels to study how APP and APOE4 interact at the cellular and molecular level to influence neurodegeneration are lacking. Here, we show that the nematodeC. eleganscan model important aspects of AD including age-related, patterned neurodegeneration that is exacerbated byAPOE4. Specifically, we found thatAPOE4, but notAPOE3, acts withAPPto hasten and expand the pattern of cholinergic neurodegeneration caused byAPP. Molecular mechanisms underlying how APP and APOE4 synergize to kill some neurons while leaving others unaffected may be unc...
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Papers by Aliyah Jushe Encarnacion