Intracellular accumulation of detergent-soluble amyloidogenic Aβ fragment of Alzheimer's disease precursor protein in the hippocampus of aged transgenic mice

Abstract

To study amyloid β-protein (Aβ) production and aggregation in vivo, we created two transgenic (Tg) mouse lines expressing the C-terminal 100 amino acids of human amyloid precursor protein (APP): Tg C100.V717F and Tg C100.WT. Western blot analysis showed that human APP-C100 and Aβ were produced in brain and some peripheral tissues and Aβ was produced in serum. Using antibodies specific for the Aβ C terminus we found that Tg C100.V717F produced a 1.6-fold increase in Aβ42/Aβ40 compared with Tg C100.WT. Approximately 30% of total brain Aβ (~122 ng/g of wet tissue) was water- soluble. The remaining 70% of Aβ partitioned into the particulate fraction and was completely sodium dodecyl sulfate-solu..