Please find enclosed the manuscript: ACE variants and risk of Alzheimer’s Disease, by Sarah Hamilton et al., to be submitted as an Original Research Article to Neurobiology of Aging. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is not under review at any other publication.

In this manuscript, we report the results of a genetic and functional study in a white population of sporadic Alzheimer’s Disease patients on the risk of suffering cognitive impairments.

We believe that our findings could be of interest to the readers of Neurobiology of Aging, because they could have a great impact on the diagnostic, prognostic and treatment of patients with Alzheimer’s Disease. Indeed, the ApoE gene is the only well recognized risk factor for Alzheimer’s Disease at the moment (Goder et al. 1998), and we report here evidence that the ACE gene could also be involved in this disease. Moreover, we show that the variant studied modulates ACE levels and increase the predictive value of the ApoE gene.

This study could thus have a great pharmacogenetic interest and bring new and important light in the field of Alzheimer’s Disease management and we hope that the editorial board and the reviewers will agree on the interest of this study.

Sincerely yours,

Sarah H. and Lucas Delphino on behalf of the authors.

Corresponding author: Lucas Delphino at Alzheimer’s Disease Laboratory, Marie Curie Research Institute, 75000, Paris, France, xxx@mariecurie.fr, phone number: +33582246xxx, fax number: +33582246xxx.