The depletion of neuronal
calcium binding proteins deprives neurons of the capacity to
buffer high levels of intracellular Ca(2+) and this leaves them vulnerable to
pathological processes, such as those present in
Alzheimer's disease (AD). The aim of the present study was to investigate the expression of the
calcium binding proteins,
calbindin-D28K,
calretinin and
parvalbumin in the dentate gyrus (DG) of
amyloid precursor
protein (APP)/
presenilin 1 (PS1) transgenic (Tg) mice and their non-Tg littermates, as well as the relation with the deposition of human
amyloid beta (Abeta). We measured the expression of these three
proteins at seven different rostro-caudal levels, and in the molecular, granular and polymorphic layers of the DG. We found that, except in the most caudal part of the DG, there is a substantial loss of
calbindin-D28K immunoreactivity in all three layers of the DG in APP/PS1 mice compared with the non-Tg mice. Significant loss of
calretinin immunoreactivity is present in most of the polymorphic layer of the DG of APP/PS1 mice compared with the non-Tg mice, as well as in the rostral and intermediate part of the inner molecular layer. Compared with the non-Tg mice
parvalbumin immunoreactivity is significantly reduced throughout the whole polymorphic layer as well as in the rostral and intermediate part of the granular layer of DG in APP/PS1 mice. The relatively preservation of
calbindin immunoreactivity in the caudal part of molecular and granular layers as well as
calretinin immunoreactivity in the caudal part of polymorphic layer of the DG is likely related to the lower Abeta expression in those parts of DG. The present data suggest an involvement of
calcium-dependent pathways in the pathogenesis of AD and indicate that there exists a subfield and layer-specific decrease in immunoreactivity which is related to the type of
calcium-binding protein in APP/PS1 mice. Moreover, it seems that APP expression affects more the
calbindin expression then
parvalbumin and
calretinin expression in the DG of APP/PS1 Tg mice.