. Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer's disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications. PLoS One. 2020;15(5):e0221669. Epub 2020 May 21 PubMed.


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  1. This study extends prior cell culture, sub-cellular biochemical, animal, and human studies that show presenilin 1 mutations have biological consequences. As demonstrated nicely here, the stem-cell-derived model can facilitate studies of how specific PS1 mutations affect cells. The authors do a nice job of demonstrating the mutation leads to cell stress, and recapitulates molecular phenomena associated with AD.

    It was certainly interesting to see the authors speculate on potential mechanisms. In this case, the scenario laid out in the discussion sought to reconcile the observed mutation-dependent cell phenomena with the amyloid cascade hypothesis. This led to speculation that the presenilin mutation increased intracellular amyloid-β oligomers, which subsequently acted as the agent of cell stress.

    A rigorous assessment of whether Aβ oligomers are a critical mediator of the various cell changes observed, or are an additional byproduct of cell stress, a link in a longer mechanistic chain, or simply an independent byproduct of the mutant presenilin would be interesting to experimentally explore.

    View all comments by Russell Swerdlow

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This paper appears in the following:


  1. Umbilical Cord With Presenilin Mutation Births New Cell Model of Familial AD


  1. PSEN1 E280A