| First Author | Niedowicz DM | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1832 |
| Issue | 3 | Pages | 439-44 |
| PubMed ID | 23274884 | Mgi Jnum | J:199052 |
| Mgi Id | MGI:5500150 | Doi | 10.1016/j.bbadis.2012.12.009 |
| Citation | Niedowicz DM, et al. (2013) Leptin regulates amyloid beta production via the gamma-secretase complex. Biochim Biophys Acta 1832(3):439-44 |
| abstractText | Alzheimer's disease (AD) is the most common age-related neurodegenerative disease, affecting an estimated 5.3million people in the United States. While many factors likely contribute to AD progression, it is widely accepted that AD is driven by the accumulation of beta-amyloid (Abeta), a small, fibrillogenic peptide generated by the sequential proteolysis of the amyloid precursor protein by the beta- and gamma-secretases. Though the underlying causes of Abeta accumulation in sporadic AD are myriad, it is clear that lifestyle and overall health play a significant role. The adipocyte-derived hormone leptin has varied systemic affects, including neuropeptide release and neuroprotection. A recent study by Lieb et al. (2009) showed that individuals with low plasma leptin levels are at greater risk of developing AD, through unknown mechanisms. In this report, we show that plasma leptin is a strong negative predictor of Abeta levels in the mouse brain, supporting a protective role for the hormone in AD onset. We also show that the inhibition of Abeta accumulation is due to the downregulation of transcription of the gamma-secretase components. On the other hand, beta-secretase expression is either unchanged (BACE1) or increased (BACE2). Finally, we show that only presenilin 1 (PS1) is negatively correlated with plasma leptin at the protein level (p<0.0001). These data are intriguing and may highlight a role for leptin in regulating the onset of amyloid pathology and AD. |
