| First Author | Roberts JA | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 46 | Pages | eabi8178 |
| PubMed ID | 34757788 | Mgi Jnum | J:387057 |
| Mgi Id | MGI:6832745 | Doi | 10.1126/sciadv.abi8178 |
| Citation | Roberts JA, et al. (2021) A brain proteomic signature of incipient Alzheimer's disease in young APOE epsilon4 carriers identifies novel drug targets. Sci Adv 7(46):eabi8178 |
| abstractText | Aptamer-based proteomics revealed differentially abundant proteins in Alzheimer's disease (AD) brains in the Baltimore Longitudinal Study of Aging and Religious Orders Study (mean age, 89 +/- 9 years). A subset of these proteins was also differentially abundant in the brains of young APOE epsilon4 carriers relative to noncarriers (mean age, 39 +/- 6 years). Several of these proteins represent targets of approved and experimental drugs for other indications and were validated using orthogonal methods in independent human brain tissue samples as well as in transgenic AD models. Using cell culture-based phenotypic assays, we showed that drugs targeting the cytokine transducer STAT3 and the Src family tyrosine kinases, YES1 and FYN, rescued molecular phenotypes relevant to AD pathogenesis. Our findings may accelerate the development of effective interventions targeting the earliest molecular triggers of AD. |
