Leptin regulates amyloid β production via the γ-secretase complex.
Publication/Presentation Date
3-1-2013
Abstract
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 β-amyloid (Aβ), a small, fibrillogenic peptide generated by the sequential proteolysis of the amyloid precursor protein by the β- and γ-secretases. Though the underlying causes of Aβ 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 Aβ levels in the mouse brain, supporting a protective role for the hormone in AD onset. We also show that the inhibition of Aβ accumulation is due to the downregulation of transcription of the γ-secretase components. On the other hand, β-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
Volume
1832
Issue
3
First Page
439
Last Page
444
ISSN
0006-3002
Published In/Presented At
Niedowicz, D. M., Studzinski, C. M., Weidner, A. M., Platt, T. L., Kingry, K. N., Beckett, T. L., Bruce-Keller, A. J., Keller, J. N., & Murphy, M. P. (2013). Leptin regulates amyloid β production via the γ-secretase complex. Biochimica et biophysica acta, 1832(3), 439–444. https://doi.org/10.1016/j.bbadis.2012.12.009
Disciplines
Medicine and Health Sciences
PubMedID
23274884
Department(s)
Fellows and Residents
Document Type
Article