Extracellular deposits of aβ produced in cultures of Alzheimer disease brain vascular smooth muscle cells

Abstract

Alzheimer disease (AD) and Down syndrome (DS) brains contain deposits of amyloid-β peptide that are located extracellularly in the neuropil and in blood vessels walls. A small fraction of brain Aβ is detected intracellularly in neurons, smooth muscle cells, and microglia. The roles of these extracellular and intracellular pools of Aβ in pathogenesis of AD-type dementia are controversial. Cell culture models of vascular amyloidosis-β revealed intracellular, but not extracellular deposition of Aβ. Here we demonstrate for the first time, formation of extracellular deposits of Aβ in primary cultures of vascular smooth muscle cells isolated from AD cases with cerebrovascular amyloid angiopathy. Extracellular Aβ deposition required the use of cultures that produced high quantities of Aβ, which contained at least 50% of cells forming intracellular Aβ deposits, and providing extracellular matrix proteins. During 12 days of culture in this system, we observed accumulation of nonfibrillar, granular deposits in extracellular matrix, similar to early stages of vascular amyloidogenesis in vivo. This is a valuable system to study the effects of various potential amyloidogenic factors on formation of extracellular Aβ deposits.