Extracellular deposits of A beta produced in cultures of Alzheimer disease brain vascular smooth muscle cells.
Alzheimer disease (AD) and Down syndrome (DS) brains contain deposits of amyloid-beta peptide that are located extracellularly in the neuropil and in blood vessels walls. A small fraction of brain Abeta is detected intracellularly in neurons, smooth muscle cells, and microglia. The roles of these extracellular and intracellular pools of Abeta in pathogenesis of AD-type dementia are controversial. Cell culture models of vascular amyloidosis-beta revealed intracellular, but not extracellular deposition of Abeta. Here we demonstrate for the first time, formation of extracellular deposits of Abeta in primary cultures of vascular smooth muscle cells isolated from AD cases with cerebrovascular amyloid angiopathy. Extracellular Abeta deposition required the use of cultures that produced high quantities of Abeta, which contained at least 50% of cells forming intracellular Abeta 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 Abeta deposits.
Frackowiak
Janusz
J
NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. Janusz.Frakowia@omr.state.ny.us
Potempska
Anna
A
LeVine
Harry
H
Haske
Taraneh
T
Dickson
Dennis
D
Mazur-Kolecka
Bozena
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D000939:Epitopes / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology; D005625:Frontal Lobe / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008578:Meninges / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D016229:Amyloid beta-Peptides; D000939:Epitopes; D010446:Peptide Fragments