PONE-D-19-26357

Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

PLOS ONE

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: Minor:

P. 4 l. 86: "...explain the dysregulation of the sleep-wake cycle characteristically observed in ". Something is missing in this sentences: AD?

please provide information on the authors contribution to the work

Reviewer #2: Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

Reviewer comments to author

A reduction in PLR in Alzheimer disease was previously described ( Tales et al., 2001; La Morgia et al., 2016). The paper by Dra. Angela J. Oh B.A. and colleagues provide evidences that the PLR and circadian rhythms are already affected in pre-symptomatic Alzheimer’s disease patients.

mRGCs decrease has been described in AD patients (La Morgia et al., 2016). The authors of this paper suggest an early mRGCs pathology before the symptoms of the disease appear, which is very interesting because using non-invasive techniques like PLR we could diagnose the disease before the symptoms manifest in the very early stages of the pathology.

Overall, the manuscript is well written and easy to follow. The experiments are convincing, the data presented is robust and the main findings are very interesting The figures are clear.

Only acomment below needs to be addressed.

Minor comments

A brief explanation of the different types of mRGCs and the possible affectation of each of these according to the results found is missing.

The different subtypes and the uneven distribution of melanopsin cells in the human retina seem to be associated with different NIF function.

Based on the results obtained in terms of PLR and circadian rhythms in AD, could you hypothesize any conclusions as to which type of mRGCs might be affected first or do you think that the loss of these cells occurs homogeneously?

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Reviewer #1: Yes: Jens Hannibal

Reviewer #2: Yes: Gema Esquiva

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Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer’s disease

PONE-D-19-26357R1

Dear Dr. Oh,

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Claudio Liguori

Academic Editor

PLOS ONE

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