성연주 (Washington University School of Medicine)

한빛사논문

조회439

Washington University School of Medicine

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Sci. Transl. Med., 5 Jul 2023 Vol 15, Issue 703 | https://doi.org/10.1126/scitranslmed.abq5923 Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer’s disease

Yun Ju Sung ^1,2,3, Chengran Yang ^1,2, JoanneNorton ^1,2, Matt Johnson ^1,2, AnneFagan ^4,5, RandallJ. Bateman ^4,5, RichardJ. Perrin ^4,5,6, JohnC. Morris ^4,5,6, MartinR. Farlow ⁷, JasmeerP. Chhatwal ⁸, Peter R. Schofield^9,10, HelenaChui ¹¹, FengxianWang ^1,2, BrennaNovotny ¹, AbdallahEteleeb ¹, Celeste Karch ^1,2, SuzanneE. Schindler ^4,5, Herve Rhinn ¹², Erik C. B. Johnson ¹³, Hamilton Se-Hwee Oh ¹⁴, Jarod Evert Rutledge ¹⁴, Eric B. Dammer ¹³, NicholasT. Seyfried ^13,15, Tony Wyss-Coray ¹⁴, OscarHarari ¹, CarlosCruchaga ^1,2,4*

¹Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108,USA.
²Neuro Genomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
³Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63108, USA.
⁴CharlesF. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
⁵Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, USA.
⁶Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO63108, USA.
⁷Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁸Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA02115, USA.
⁹Neuroscience Research Australia, Randwick, NSW 2031, Australia.
¹⁰School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
¹¹Department of Neurology, University of Southern California, Los Angeles, CA 90089, USA.
¹²Leal Therapeutics,17 BridenSt., Office329, Worcester, MA 01605, USA.
¹³Goizueta Alzheimer’s Disease Research Center, Emory University School of Medicine, Atlanta, GA30329, USA.
¹⁴Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA.
¹⁵Department of Biochemistry, Emory School of Medicine, Atlanta, GA 30329, USA.

*Corresponding author: correspondence to CarlosCruchaga

Abstract

Proteomic studies for Alzheimer’s disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic AD cases. Here, we present a proteomic study analyzing 1305 proteins in brain tissue, cerebrospinal fluid (CSF), and plasma from patients with sporadic AD, TREM2 risk variant carriers, patients with autosomal dominant AD (ADAD), and healthy individuals. We identified 8 brain, 40 CSF, and 9 plasma proteins that were altered in individuals with sporadic AD, and we replicated these findings in several external datasets. We identified a proteomic signature that differentiated TREM2 variant carriers from both individuals with sporadic AD and healthy individuals. The proteins associated with sporadic AD were also altered in patients with ADAD, but with a greater effect size. Brain-derived proteins associated with ADAD were also replicated in additional CSF samples. Enrichment analyses highlighted several pathways, including those implicated in AD (calcineurin and Apo E), Parkinson’s disease (α-synuclein and LRRK2), and innate immune responses (SHC1, ERK-1, and SPP1). Our findings suggest that combined proteomics across brain tissue, CSF, and plasma can be used to identify markers for sporadic and genetically defined AD.

논문정보

형식Research article
게재일2023년 07월 (BRIC 등록일 2023-07-10)
연구진국외 연구진
분야 의약학 > 응용의학

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