Increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimer's disease
Katarina Kagedal, Woojin Scott Kim, Hanna Appelqvist, Sharon Chan, Danni Cheng, Lotta Agholme, Kevin Barnham, Heather McCann, Glenda Halliday, Brett Garner
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | ELSEVIER | Published : 2010
The Niemann-Pick type C1 (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimer's disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, a..View full abstract
Awarded by Australian National Health and Medical Research Council
This study was supported by a fellowship from the Swedish Research Council and grants from the foundations of Nilsson, Engkvist and Wiberg (KK) and project grant 510148 from the Australian National Health and Medical Research Council (BG). We are very grateful to Assoc Prof Andrew Hill for provision of the CHO-APP cell line and to Prof Colin Masters and Dr Qiao-Xin Li for providing WO2 antibody. Human brain tissues were obtained from the Australian Brain Donor Programs Prince of Wales Medical Research Institute Tissue Resource Centre and the NSW Tissue Resource Centre.