| First Author | Kummer MP | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 49 | Pages | 17824-9 |
| PubMed ID | 23223301 | Mgi Jnum | J:193190 |
| Mgi Id | MGI:5467881 | Doi | 10.1523/JNEUROSCI.1504-12.2012 |
| Citation | Kummer MP, et al. (2012) Mrp14 deficiency ameliorates amyloid beta burden by increasing microglial phagocytosis and modulation of amyloid precursor protein processing. J Neurosci 32(49):17824-9 |
| abstractText | Neuroinflammation plays a fundamental role in the pathogenesis of Alzheimer's disease (AD), resulting in the extensive activation of microglial and astroglial cells. Here we describe the role of myeloid-related protein Mrp14, a recently described amplifier of inflammation, in Alzheimer's disease and in the related amyloid precursor protein/presenilin1 (APP/PS1) mouse model. Detection of Mrp14 in control, mildly cognitive impaired, and AD patients revealed a strong induction of Mrp14 in protein extracts as well as in the cerebrospinal fluid, but not in blood plasma. In APP/PS1 mice, Mrp14 and its heterodimeric partner Mrp8 was found to be upregulated in microglial cells surrounding amyloid plaques. Functionally, loss of Mrp14 led to increased phagocytosis of fibrillar amyloid beta (Abeta) in microglia cells in vitro and in vivo. Generating APP/PS1-transgenic mice deficient for Mrp14, we observed a decrease of key cytokines involved in APP processing, a reduction of BACE1 expression and activity, and consequently overall Abeta deposition. We therefore conclude that Mrp14 promotes APP processing and Abeta accumulation under neuroinflammatory conditions. |
