Pltp Deficiency Impairs Learning And Memory Capabilities Partially Due To Alteration Of Amyloid-Beta Metabolism In Old Mice

Increased expression of phospholipid transfer protein (PLTP) was observed in the brains of Alzheimer's disease (AD) patients; however, the role of PLTP in the progress of AD is still poorly understood. The objective of this study was to evaluate the effect of PLTP deficiency on the recognition and metabolism of amyloid-beta (A beta) in mice. We performed the Morris water maze to determine the learning and memory capabilities of 50-week age wild type mice (WT, n = 12) and PLTP knockout mice (PLTP-/-, n = 12). The levels of A beta and amyloid-beta protein precursor (A beta PP) were examined by ELISA and western blot, respectively. The levels and activity of beta- and gamma-secretases were determined by western blot and activity assay kit, respectively. Morris water maze results showed that PLTP deficiency significantly impaired recognition compared with WT mice. Levels of A beta(42) in the cortex and hippocampus was significantly increased, yet the levels of A beta(40) in the cortex was decreased in PLTP-/- compared with WT mice. No typical senile plaques were found in the WT or PLTP-/- mice. A beta PP expression and beta-secretase activity were both significantly increased in PLTP-/- mice. Moreover, PLTP deficiency increased the expression of gamma-secretase catalytic units and decreased the content of apolipoprotein E. Therefore we concluded that PLTP deficiency impaired cognition and aggravated AD by enhancing the generation of A beta in the cortex of old mice.