| First Author | Sutcliffe JG | Year | 2011 |
| Journal | J Neurosci Res | Volume | 89 |
| Issue | 6 | Pages | 808-14 |
| PubMed ID | 21374699 | Mgi Jnum | J:283974 |
| Mgi Id | MGI:6390209 | Doi | 10.1002/jnr.22603 |
| Citation | Sutcliffe JG, et al. (2011) Peripheral reduction of beta-amyloid is sufficient to reduce brain beta-amyloid: implications for Alzheimer's disease. J Neurosci Res 89(6):808-14 |
| abstractText | Three loci that modify beta-amyloid (Abeta) accumulation and deposition in the brains of a mouse model of Alzheimer's disease have been previously described. One encompasses the Psen2 gene encoding presenilin 2, a component of the gamma-secretase activity responsible for generating Abeta by proteolysis. We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Abeta deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Abeta in both the blood and the brain, confirming brain Abeta's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease. The genes Cib1 and Zfhx1b reside within the other modifier loci and also exhibit heritable expression in the liver, suggesting that they too contribute to Abeta accumulation. |
