Neurons from mutant hiPSC lines express PSEN1-A246E mutations themselves and show AD-like biochemical features, that is, amyloidogenic processing of amyloid precursor protein (APP) indicated by an increase in β-amyloid (Aβ)42/Aβ40 ratio.
Susceptibility to diet-induced obesity and glucose intolerance in the APP (SWE)/PSEN1 (A246E) mouse model of Alzheimer's disease is associated with increased brain levels of protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4), and basal phosphorylation of S6 ribosomal protein.
PS1/A246E mice mimic to some extent pre-symptomatic Alzheimer's disease neuropathology, useful for studying early neurochemical changes often inaccessible in clinical studies.
Transgenic mice carrying both the human amyloid precursor protein (APP) with the Swedish mutation and the presenilin-1 A246E mutation (APP/PS1 mice) develop Alzheimer's disease-like amyloidbeta protein (Abeta) deposits around 9 months of age.
To test whether oxidative stress is an inherent property of AD tissues, the ability of cultured fibroblasts bearing the AD Presenilin-1 246 Ala-->Glu mutation to handle reactive oxygen species (ROS) was compared to controls.