Why Have the Benefits of DHA Not Been Borne Out in the Treatment and Prevention of Alzheimer’s Disease? A Narrative Review Focused on DHA Metabolism and Adipose Tissue

Round 1

Reviewer 1 Report

Dear Authors

Dear Authors

The manuscript here is a review based on a "hot topic" of medicinal chemistry field and medicine; It's within the aim and scope of the journal in a broad sense and really interesting for a large range of audience.The organization is clear and easily readable, thus my recommendation is to publish as is.

Author Response

We are incredibly grateful to the reviewer for their positive comments and are glad that they feel it is a meaningful and interesting contribution.

Reviewer 2 Report

The review article written by Health and Wood is a exceedingly well written text that provides excellent background on the biochemistry of DHA and addresses important clinical aspects of dietary and supplemental DHA in treatment and prevention of AD.

In particular, the authors highlight poorly understood aspects of DHA, including mechanism of DHA flux between diet, plasma and adipose, and the contribution of adipose-derived DHA to brain DHA levels. And how metabolic dysfunction may impair the flux of DHA between plasma, adipose and brain.

This is a well constructed, comprehensive review; I have no additional text suggestions. 

I only have a two considerations related to figures.

First, one minor suggestion relates to the figure location.  Currently, the figures are contained within the first section of the review.  However, they are most relevant beginning in section 4 and it could be useful to have the figures available at that location. 

Second, it may be useful to have a figure that illustrates the proposed protective effects of DHA on AD (connected to Section 2) 

Author Response

We are incredibly grateful to the reviewer for their positive comments. We have moved the figures up to section 4 as suggested.

We also appreciated the suggestion of an additional figure on the proposed beneficial effects of DHA in AD. However, at length, we decided that we were unable to provide a novel and meaningful graphic depiction of these processes within the requested time scale of revision. Importantly, this was not the key focus of our manuscript, and we highlight other contributions to the field that provide summary figures of the mechanisms involved in DHA neuroprotection.