Cerebral Folate Metabolism in Post-Mortem Alzheimer’s Disease Tissues: A Small Cohort Study

Round 1

Reviewer 1 Report

Dear Authors, the manuscript entitled Cerebral Folate Metabolism in Post-Mortem Alzheimer’s Disease Tissues: A Small Cohort Study describes an interesting study about folate changes in AD patients. It provides new interesting information about the complexity of AD neurodegeneration related to folate metabolism, which may point to an interesting treatment target. 

It is a well-planned and executed study, it is a well-written manuscript with a correct methodology, the discussion is appropriate and the results are in accordance with the experiments carried out. The conclusion is reasonable due to its limitations correctly explained by the authors.

I consider this manuscript of good scientific quality, with results that are of interest in AD knowledge. Therefore, I recommend its publication in the journal.

Reviewer 2 Report

The manuscript entitled “Cerebral folate metabolism in post-mortem Alzheimer’s disease tissues: a small cohort study” by Naz et al., is well designed to investigate the cerebral folate system in post-mortem brains and matched cerebrospinal fluid (CSF) samples from subjects with definite Alzheimer’s disease (AD) and normal brains using immunohistochemistry, western blot and dot blot. reduction of FDH in CSF prohibits FRα-folate entry via FDH-positive astrocytes and promotes entry through the GFAP path-way directly to neurons for hypermethylation. Although, the study had limitations of using small post-mortem samples the authors tried to explained that the cognitive decline not only cause of neurons. Such suggestion may help to go for a larger and more detailed study of cerebral metabolism in AD.