Functional Glial Activation Mediates Phenotypic Effects of APOEɛ4 and Sex in Alzheimer’s Disease

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Reviewer 1:

 

The Authors present the results of a study examining the impact of APOEɛ4 allele frequency and sex on the phenotype of Alzheimer's disease, focusing on functional glial activation and its role in early clinical Alzhimers Disease. The topic is interesting and seems to be important bearing in mind the scope for early disease diagnosing in AD patients and preventing the complications of AD at early stage. The experiments were designed and conducted via interesting ways and performed in accordance with suitable methods with necessary statistical analysis.

 

Question 1: Are there any preclinical studies that evaluated these effects in animal models? If yes please cite the relevant references in the introduction.

Question 2: The authors have provided detailed information about the impact of genetic variation, specifically the APOEɛ4 allele, on the development and progression of AD in individuals below the age of 75 years. ​ It discusses how factors such as genotype, sex, and age influence glial activation, amyloid and tau pathology, neurodegeneration, and clinical features in early clinical AD populations. ​However, it might be interesting for the readers if the authors can discuss the APOEɛ4 allele frequency, sex, glial activation, biomarkers, and cognitive outcomes in early clinical AD populations aged 50-74. ​

 Question 3: Does glial cell expression vary with the genetics and sex? If yes please add relevant citations and discuss briefly.

Question 4: What are the differences in cognitive deficits between male and female participants?

Question 5: I suggest the authors to briefly describe about the future direction for AD diagnosis with APOEɛ4 allele frequency and what measures are necessary for proper clinical translation of this finding ?

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript is described about the correlation between functional glial acitviation and apoE4 isoform. The authors present a careful and thorough analysis of ApoE isoform on the phenotype of Alzheimer's disease. I believed that many researchers concerned with Alzheimer's disease is interested in this conclusion.   

Author Response

Comment 1. ....many researchers concerned with Alzheimer's disease is interested in this conclusion. 

Response 1. We agree with Reviewer 2 and thank him/her for his comment.

Author Response File: Author Response.pdf