Secretion and accumulation of Aβ by brain vascular smooth muscle cells from AβPP-Swedish transgenic mice

Abstract

Alzheimer amyloid-β is deposited in the neuropil and in brain blood vessels in transgenic Tg2576 mice that overexpress human amyloid-β precursor protein (AβPP) containing the Swedish mutation (AβPP-Swe). Because the AβPP transgene in Tg2576 mice is placed behind the PrP promoter, all amyloid-β, including vascular amyloid, is considered to be of neuronal origin. We studied the expression of the transgenic AβPP in smooth muscle cells cultured from brain blood vessels from Tg2576 mice. We found that brain vascular smooth muscle cells overexpressed human AβPP-Swe approximately 4 times the physiological levels of mouse AβPP. The cultured cells secreted abundant Aβ1-40 and Aβ1-42 and formed intracellular Aβ-immunoreactive granules. The percentage of cells containing intracellular Aβ and the amount of intracellular Aβ were significantly higher in cultures obtained from 14-month-old than from 4-month-old mice, as tested on first or second passages. During cell senescence in culture, intracellular accumulation of Aβ and C-terminal fragments of AβPP increased in cells derived from both 4- and 14-month-old mice. Vascular muscle cells from Tg2576 mice appear to be a valuable model of the intracellular accumulation of Aβ. We suggest that vascular muscle cells may be involved in the production of cerebro-vascular amyloid in Tg2576 mice.