-Induced Patterned Neurodegeneration Is Exacerbated by in .

Genetic and epidemiological studies have found that variations in the amyloid precursor protein () and the apoliopoprotein E () genes represent major modifiers of the progressive neurodegeneration in Alzheimer's disease (AD). An extra copy of or gain-of-function mutations in correlate with early onset AD. Compared to the other variants ( and ), the ε4 allele of () hastens and exacerbates early and late onset forms of AD. Convenient 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 can model important aspects of AD including age-related, patterned neurodegeneration that is exacerbated by Specifically, we found that , but not , acts with to hasten and expand the pattern of cholinergic neurodegeneration caused by 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.