I pull up a peer review I received on a grant application every once in a while as a teaching moment for students. One hypothesis of the grant was that misfolding of full length amyloid precursor protein (APP), in addition to it’s famous cleavage product amyloid beta, may contribute to neuronal dysfunction in Alzheimer’s Disease. The details aren’t important. The important bit it that it challenged (slightly) the amyoid cascade hypothesis. I got this gem in return:
Any hypothesis of AD involving intraneuronal APP aggregation must also propose a central role for Abeta42.
and to continue…..
Because the PI’s hypothesis is flawed, the work plan has minimal merit
I was a relatively new PI as this point. Way to kill my spirit. This post inspired by this tweet by @GertyZ: