Blood–Brain Barrier Dysfunction and Aβ42/40 Ratio Dose-Dependent Modulation with the ApoE Genotype within the ATN Framework
Round 1
Reviewer 1 Report
This paper presents the work of the authors on investigating the relationship between blood-brain barrier (BBB) damage biomarkers and Alzheimer’s disease (AD) biomarkers from cerebrospinal fluid (CSF). The goal of the authors is to determine if BBB damage biomarkers can be reliable predictors of AD and cognitive impairment. The authors conducted the study on 172 patients with memory impairment classified within the (Amyloid-Tau-Neurodegeneration) ATN framework. They did not find any correlation between BBB damage biomarkers and ATN type of the patients, or Mini Mental State Examination (MMSE) scores. However, if BBB damage was classified using CSF/Serum albumin index (Qalb), there was a negative correlation with Aβ40 levels. Overall, the paper is well written and presents the results in a clear and logical fashion. The authors also point out some limitations of their study, such as the small sample size, and the fact that all the patients had memory loss and therefore a suitable physiological control might be missing. While it would be hard for me to say that the results of the paper are exciting, they are still a useful contribution to the field.
Author Response
Dear Reviewer,
We would like to thank you for your valuable comments. We appreciate that the negative findings of the cross-sectional correlation between ATN biomarkers and BBB markers are far from exciting, but also agree that these types of studies are needed in the field.
Reviewer 2 Report
The present research article by Toniolo et al. entitled “Blood-brain-barrier dysfunction and Aβ42/40 ratio dose-dependent modulation by ApoE genotype within the ATN framework” demonstrates the systematic evaluation of CSF for AD-biomarkers from a cohort of cognitively impaired individuals and correlate the data on BBB dysfunction, demographics and ApoE status. Authors also showed the significance of ApoE status for a dose-dependent effect on the Aβ42/40 ratio. The study has been conducted meticulously. Experiments and data interpretation in this study have been systematically carried out that support the key findings and conclusions drawn in this study.
English is fine. There are several minor typographical errors that need to be corrected.
Author Response
Dear Reviewer,
We thank you for the very valuable feedback. We will revise the typographical errors accordingly.