Amyloid pathology-produced unexpectedmodifications of calcium homeostasis in hippocampal subicular dendrites

Introduction: Alzheimer's disease (AD) is linked to neuronal calcium dyshomeostasis, which is associated with network hyperexcitability. Decreased expression of the calcium-binding protein cal-bindin-D-28K (CB) might be a susceptibility factor for AD. The subiculum is affected early in AD, for unknown reasons. Methods: In AD, CB knock-out and control mice fluorescence Ca2+ imaging combined with patch clamp were used to characterize Ca2+ dynamics, resting Ca2+, and Ca2+-buffering capacity in subicular neurons. CB expression levels in wild-type and AD mice were also analyzed. Results: The subiculum and dentate gyrus of wild-typemice showed age-related decline in CB expression not observed in AD mice. Resting Ca2+ and Ca2+-buffering capacity was increased in aged AD mice subicular dendrites. Modeling suggests that AD calcium changes can be explained by alterations of Ca2+ extrusion pumps rather than by buffers. Discussion: Overall, abnormal Ca2+ homeostasis in AD has an age dependency that comprises multiplemechanisms, including compensatory processes.