Amyloid pathology-produced unexpected modifications 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 Ca ²⁺ imaging combined with patch clamp were used to characterize Ca ²⁺ dynamics, resting Ca ²⁺ , and Ca ²⁺ -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-type mice showed age-related decline in CB expression not observed in AD mice. Resting Ca ²⁺ and Ca ²⁺ -buffering capacity was increased in aged AD mice subicular dendrites. Modeling suggests that AD calcium changes can be explained by alterations of Ca ²⁺ extrusion pumps rather than by buffers.
Discussion: Overall, abnormal Ca ²⁺ homeostasis in AD has an age dependency that comprises multiple mechanisms, including compensatory processes.
(© 2019 the Alzheimer's Association.)