| First Author | Tong Y | Year | 2015 |
| Journal | Hum Mol Genet | Volume | 24 |
| Issue | 19 | Pages | 5388-403 |
| PubMed ID | 26160914 | Mgi Jnum | J:318357 |
| Mgi Id | MGI:6859343 | Doi | 10.1093/hmg/ddv262 |
| Citation | Tong Y, et al. (2015) Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer's disease. Hum Mol Genet 24(19):5388-403 |
| abstractText | Phospholipid transfer protein (PLTP) is a widely expressed lipid transfer protein participating in the transport of cholesterol and other lipids in the plasma and peripheral tissues. Recently, elevated amyloid beta (Abeta) in young and aged PLTP-deficient brains had been reported. However, the role of PLTP in amyloid precursor protein (APP) processing and Alzheimer's disease (AD) pathology remains elusive. Here we first found that deficiency of PLTP accelerated memory dysfunction in APP/PS1DeltaE9 AD model mice at the age of 3 months. Further characterization showed that PLTP deficiency increased soluble Abeta peptides, and intracellular accumulation of Abeta was illustrated, which might be due to disrupted APP turnover and the enhanced amyloidogenic pathway. Besides, reduced brain-derived neurotrophic factor (BDNF) was found in PLTP-deficient APP/PS1DeltaE9 mice, and the BDNF level was negatively correlated with Abeta42 content, instead of Abeta40 content. In addition, autophagic dysfunction was found in the PLTP-deficient APP/PS1DeltaE9 mice. Our data presented a novel model to link phospholipid metabolism to APP processing and also suggested that PLTP played an important role in Abeta metabolism and would be useful to further elucidate functions of PLTP in AD susceptibility. |
