Late age increase in soluble amyloid-beta levels in the APP23 mouse model despite steady-state levels of amyloid-beta-producing proteins
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Biochimica et biophysica acta : molecular basis of disease. - Amsterdam
, p. 105-112
University of Antwerp
Age is considered the most important risk factor for Alzheimer's disease. Soluble amyloid-beta (Aβ) has been implicated as the primary neurotoxic agent in Alzheimer's disease pathology. The link between aging and Aβ, however, remains unclear. In this study, we aimed to investigate the evolution of soluble Aβ over various age groups in the APP23 amyloidosis mouse model and correlate these changes to alterations in the levels of proteins involved in Aβ production. We found a distinct pattern with an initial buildup of Aβ which could be linked to an increase in amyloid precursor protein (APP). Following this increase, Aβ concentrations remained stable until a surge in Aβ142 at 18 months. This rise was followed by an increase in Aβ140 and overall Aβ levels. The rise in Aβ at later age did not correlate to changes in the levels of APP, presenilin, and β-secretase and is suggested to result from a decrease in clearance. The APP23 model could provide an interesting tool for future research regarding aging and Aβ clearance.