X11α haploinsufficiency enhances Aβ amyloid deposition in Alzheimer's disease transgenic mice |
| |
Authors: | Inderjeet Saluja Henry Paulson Ashwin Gupta R. Scott Turner |
| |
Affiliation: | aDepartment of Neurology, University of Michigan, USA;bVA GRECC, Ann Arbor, MI, USA |
| |
Abstract: | The neuronal adaptor protein X11α/mint-1/APBA-1 binds to the cytoplasmic domain of the amyloid precursor protein (APP) to modulate its trafficking and metabolism. We investigated the consequences of reducing X11α in a mouse model of Alzheimer's disease (AD). We crossed hAPPswe/PS-1ΔE9 transgenic (AD tg) mice with X11α heterozygous knockout mice in which X11α expression is reduced by approximately 50%. The APP C-terminal fragments C99 and C83, as well as soluble Aβ40 and Aβ42, were increased significantly in brain of X11α haploinsufficient mice. Aβ/amyloid plaque burden also increased significantly in the hippocampus and cortex of one year old AD tg/X11α (+/−) mice compared to AD tg mice. In contrast, the levels of sAPPα and sAPPβ were not altered significantly in AD tg/X11α (+/−) mice. The increased neuropathological indices of AD in mice expressing reduced X11α suggest a normal suppressor role for X11α on CNS Aβ/amyloid deposition. |
| |
Keywords: | Amyloid precursor protein Aβ Amyloid X11α Mint-1 APBA-1 Alzheimer's disease Knockout mice Transgenic mice |
本文献已被 ScienceDirect 等数据库收录! |