Hartman RE, Wozniak DF, Nardi A, Olney JW, Sartorius L, Holtzman DM. Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology. Exp Neurol. 2001 Aug;170(2):326-44. PubMed Abstract

REAGENTS/MATERIAL:
Human apoE TG mice were generated in which human apoE3 or E4 was expressed in astrocytes under the control of a GFAP promoter. For this experiment GFAP-apoE3 and GFAP-apoE4 mice hemizygous for the transgene (1/2) were bred to apoE O mice on a C57BL/6J (B6) background. The pups (all F4 generation) were apoE3 1/2, apoE4 1/2, or apoE 2/2 and had been bred back onto a B6 background for four generations and expressed no mouse apoE. For tissue analysis, Western blot analysis, levels of apoE, synaptophysin, GFAP, neuron-specific enolase, and microtubule-associated protein-2 (MAP-2) in brain tissue were determined by semiquantitative Western blotting

FUTURE DIRECTION:
The present study suggest that apoE may also influence the cognitive decline observed in AD and/or in advancing age through additional mechanisms. To help clarify this and other issues, it will be important for future research to reassess, whether the apoE4 genotype leads to profound working memory deficits and/or changes in emotionality and to establish when these alterations in behavioral function become manifest.