A brain proteomic signature of incipient Alzheimer’s disease in young APOE ε4 carriers identifies novel drug targets

Author:

Roberts Jackson A.12ORCID,Varma Vijay R.1,An Yang3,Varma Sudhir4ORCID,Candia Julián56ORCID,Fantoni Giovanna7,Tiwari Vinod8ORCID,Anerillas Carlos9ORCID,Williamson Andrew1,Saito Atsushi10,Loeffler Tina11,Schilcher Irene11,Moaddel Ruin12ORCID,Khadeer Mohammed12,Lovett Jacqueline12,Tanaka Toshiko6ORCID,Pletnikova Olga1013,Troncoso Juan C.1014,Bennett David A.15ORCID,Albert Marilyn S.14,Yu Kaiwen16ORCID,Niu Mingming16ORCID,Haroutunian Vahram1718ORCID,Zhang Bin19ORCID,Peng Junmin16ORCID,Croteau Deborah L.8ORCID,Resnick Susan M.3,Gorospe Myriam9ORCID,Bohr Vilhelm A.8ORCID,Ferrucci Luigi6ORCID,Thambisetty Madhav1ORCID

Affiliation:

1. Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

2. Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032.

3. Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

4. HiThru Analytics, Laurel, MD 20707, USA.

5. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

6. Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

7. Clinical Research Core, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

8. Section on DNA Repair, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.

9. Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

10. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

11. QPS Austria GmbH, Parkring 12, 8074 Grambach, Austria.

12. Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

13. Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA.

14. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

15. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.

16. Departments of Structural Biology and Developmental Neurobiology, Center for Proteomics and Metabolomics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.

17. Departments of Psychiatry and Neuroscience, The Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

18. Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY 10468, USA.

19. Department of Genetics and Genomic Sciences and Department of Pharmacological Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Abstract

Brain proteins altered in young APOE ε4 carriers are found decades later in Alzheimer’s disease and present novel drug targets.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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