Authors: Sergio L. Angulo, Thomas Henzi, Samuel A. Neymotin, Manuel D. Suarez, William W. Lytton, Beat Schwaller, Herman Moreno
Published: 2019-10-24
DOI: 10.1016/j.jalz.2019.07.017
Source: Full article
AbstractIntroductionAlzheimer's disease (AD) is linked to neuronal calcium dyshomeostasis, which is associated with network hyperexcitability. Decreased expression of the calcium‐binding protein cal‐ bindin‐D28K (CB) might be a susceptibility factor for AD. The subiculum is affected early in AD, for unknown reasons.MethodsIn 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.ResultsThe 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.DiscussionOverall, abnormal Ca2+ homeostasis in AD has an age dependency that comprises multiple mechanisms, including compensatory processes.