Abstract: SA-PO733
Renal Epithelia Regulate Clearance and Homeostasis of Amyloid-β
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Tampe, Bjoern, University Medical Center Goettingen, Goettingen, Germany
- Zeisberg, Michael, University Medical Center Goettingen, Goettingen, Germany
Background
Accumulation of circulating amyloid-β (Aβ) molecules is associated with accelerated Aβ deposition in the brain, thereby accelerating cognitive impairment and dementia. Aβ molecules undergo renal clearance to ensure proper Aβ homeostasis. In chronic kidney disease (CKD), impaired kidney function contributes to accumulation of circulating Aβ and accelerates cognitive impairment. Based on these prerequisites, we here aimed to elucidate molecular mechanisms contributing to impaired renal clearance of Aβ molecules.
Methods
Aβ transporters including P-glycoprotein, LRP1, LRP2 and RAGE were analyzed in multiple mouse models of acute/chronic renal failure, human kidneys and cultures of tubular epithelial cells. Genome-wide array datasets was analyzed using NephroSeq database (GSE69438).
Results
We show that Aβ transporters including P-glycoprotein, LRP1, LRP2 and RAGE are present and polarized in tubular compartments in the kidney. Progressive CKD is associated with loss and/or mislocalization of tubular Aβ transporters, implicating that tubular clearance regulates Aβ homeostasis. Finally, analysis of human kidneys and genome-wide array datasets confirmed that Aβ transporters are equally present in human renal epithelia and lost during progressive CKD.
Conclusion
In summary, we here show that Aβ transporters are present and polarized in tubular compartments in the kidney. Furthermore, we provide evidence that CKD is associated with loss of tubular Aβ transporters and impaired renal Aβ clearance. Because impaired kidney function contributes to accumulation of circulating Aβ and accelerates cognitive impairment, these findings provide insights into molecular mechanisms underlying clearance and homeostasis of Aβ.