Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits.

ABSTRACT: Transgenic mice expressing human amyloid precursor proteins (hAPP) and amyloid-beta peptides (Abeta) in neurons develop phenotypic alterations resembling Alzheimer's disease (AD). The mechanisms underlying cognitive deficits in AD and hAPP mice are largely unknown. We have identified two molecular alterations that accurately reflect AD-related cognitive impairments. Learning deficits in mice expressing familial AD-mutant hAPP correlated strongly with decreased levels of the calcium-binding protein calbindin-D28k (CB) and the calcium-dependent immediate early gene product c-Fos in granule cells of the dentate gyrus, a brain region critically involved in learning and memory. These molecular alterations were age-dependent and correlated with the relative abundance of Abeta1-42 but not with th

SUBMITTER: Palop JJ 

PROVIDER: S-EPMC170959 | biostudies-literature | 2003 Aug

REPOSITORIES: biostudies-literature