Sotiropoulos et al. investigated the impact of stress, amyloid, and glucocorticoids on tau phosphorylation and behavioral performance in rats. Although I think the paper is relevant to current research directions, the data as presented are troubling. The method for administering amyloid is unconventional and completely uncontrolled. The latter is a big problem because in this case, the peptide was administered by ICV mini-pump for 14 days. There is no mention that control animals received mock pumps or manipulations (e.g., anesthesia, etc.) of any kind. The photomicrographs do not demonstrate the effects discussed, and methods for scoring them are inadequate (score 0.5-5 by visual examination by independent investigator).

Unfortunately, this paper does little to advance our understanding of how stress can contribute to AD.

View all comments by Robert Rissman

In rereading the methods, I withdraw my statement about the pumps not being controlled. The methods mention "or vehicle" which comprised sterile distilled water. I apologize for this mistake. Other than this, I stand by the remainder of my comments.

View all comments by Robert Rissman