%0 Journal Article %J J Alzheimers Dis %D 2016 %T Diminished CRE-Induced Plasticity is Linked to Memory Deficits in Familial Alzheimer's Disease Mice. %A Bartolotti, Nancy %A Segura, Laura %A Lazarov, Orly %K Alzheimer Disease %K Animals %K Cyclic AMP Response Element-Binding Protein %K Disease Models, Animal %K Hippocampus %K Maze Learning %K Memory Disorders %K Mice %K Neuronal Plasticity %K Neurons %K Phosphorylation %X

The mechanism underlying impaired learning and memory in Alzheimer's disease is not fully elucidated. The phosphorylation of cyclic-AMP response element binding protein (pCREB) in the hippocampus is thought to be a critical initiating step in the formation of long-term memories. Here, we tested CRE-driven gene expression following learning in mice harboring the familial Alzheimer's disease-linked APPswe/PS1ΔE9 mutations using CRE-β galactosidase reporter. We show that young adult APPswe/PS1ΔE9 mice exhibit impaired recognition memory and reduced levels of pCREB, and its cofactors CREB binding protein (CBP) and p-300 following a learning task, compared to their wild type littermate counterparts. Impairments in learning-induced activation of CREB in these mice are manifested by reduced CRE-driven gene transcription. Importantly, expression of the CRE-driven immediate early gene, Egr-1 (Zif268) is decreased in the CA1 region of the hippocampus. These studies implicate defective CREB-dependent plasticity in the mechanism underlying learning and memory deficits in Alzheimer's disease.

%B J Alzheimers Dis %V 50 %P 477-89 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26682682?dopt=Abstract %R 10.3233/JAD-150650