Reduced neuronal co-localisation of nardilysin and the putative [alpha]-secretases ADAM10 and ADAM17 in Alzheimer's disease and Down syndrome brains

• Published in: GeroScience 2009-03, Vol.31 (1), p.11
• Main Authors: Bernstein, Hans-gert, Stricker, Rolf, Lendeckel, Uwe, Bertram, Iris, Dobrowolny, Henrik, Steiner, Johann, Bogerts, Bernhard, Reiser, Georg
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Down syndrome
• ISSN: 2509-2715; 2509-2723
• DOI: 10.1007/s11357-008-9076-x

The peptidase nardilysin is involved in degradation of neuropeptides and limited intracellular proteolysis. Recent reports point to an involvement of nardilysin in the pathophysiology of Alzheimer's disease. Nardilysin enhances the α-secretase activity of the disintegrin and metalloproteases (ADAMs) 10 and 17, thereby possibly contributing to reduced generation of amyloidogenic fragments from the amyloid precursor protein. A prerequisite for the α-secretase-stimulating effect of nardilysin on the activity of ADAMs in vivo is cellular co-expression of nardilysin with ADAM10 and/or ADAM17. We immunolocalised nardilysin, ADAM10, and ADAM17 in cortical regions of normal aged brain, in Alzheimer's disease, and in Down syndrome brains and counted the number of protease-expressing neurons. A considerable portion of neurons co-express nardilysin together with either ADAM10 or ADAM17. Compared to controls, in Alzheimer's disease and in Down syndrome brains there is a decreased cellular expression of all three antigens, and a reduction in the number of those neurons that co-express nardilysin with ADAM10 or with ADAM17. Our data are consistent with the notion that the proposed α-secretase-enhancing activity of nardilysin might play a role in human brain pathology.[PUBLICATION ABSTRACT]