Amyloid pathology-produced unexpected modifications of calcium homeostasis in hippocampal subicular dendrites

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.

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.

The subiculum and dentate gyrus of wild-type mice 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.

Overall, abnormal Ca²⁺ homeostasis in AD has an age dependency that comprises multiple mechanisms, including compensatory processes.