Peer-reviewed by 2 reviewers with median rating of 13.5/20. Review process was triple-blinded.
Round 1 (13/20)
Round 2 (13.5/20)
Conceptual advance and Impact5
The authors addressed an important question in this manuscript. In the reviewer's opinion, additional data should be provided to better support the conclusions made in this manuscript.
"In accordance with a recent report, low-level de novo BIN1 expression can be observed in a subset of neurons in the AD brain." This should be shown by double immunofluorescence staining using neuronal markers such as NeuN.
see comment above
Results & Discussion
In this work, the authors applied antibody tau2 which is directed against both phosphorylated and unphosphorylated tau species. No double immunofluorescence stainings assessing the distribution of tau and BIN1 in one single section are presented beside "co-stainings" using unspecific Thio S beta-sheet staining. The authors should address this issue to support their results given the possibility that tau may still colocalize with BIN1, e.g. in a pretangle state (which may histologically very much display a "punctate" pattern). Ideally, additional tau antibodies specifically directed p-tau may be applied (although in the reviewer's opinion not a prerequisite for publication).
see comments above
Conceptual advance and Impact7
Holler et al done promising work in AD filed for the MS entitled "BIN1 localization is distinct from Tau tangles in Alzheimer’s disease". Proposed conclinding remarks may add little findings in this filed.
Thank you for giving this oppurtunity.
*The reviewer has left it's name here, it was removed by the editorial team to ensure triple blindness
1.The function of BIN1 in the brain and the mechanism(s) by which AD-associated BIN1 alleles increase the risk for the disease are not known.
2. BIN1 expression and Tau propagation
Please re-write these lines.
BIN1 association with Ab need to add in 2-3 lines if any
Results & Discussion
Our results presented here are in accordance to this later report as we found a lack of overlap between neurofibrillary tangles and BIN1 immunoreactivity by immunofluorescence analysis. in this statement "of this later report", could not able to coney exact message.
what part of the brain (BA?) is used for BIN1 immunostaining