Role of perivascular cells and myocytes in vascular amyloidosis.
Amyloidogenic processing of amyloid-beta precursor protein (APP) by cells of the brain is the major pathologic component of Alzheimer's disease. Amyloid-beta (A beta) is of heterogeneous origin. Perivascular cells of monocyte-macrophage-microglial cell lineage produce fibrillar A beta in the wall of capillaries, whereas parenchymal microglial cells produce fibrillar A beta in the parenchyma of gray matter. Fibrillar A beta deposition by perivascular cells lead to endothelial cell degeneration and death, obliteration of affected capillaries, and reduction of the length of the vascular network. These changes cause local ischemia with neuronal degeneration and death. Smooth muscle cells are the source of A beta in the tunica media of parenchymal and leptomeningeal arteries and veins. Fibrillar A beta in the tunica media of leptomeningeal and parenchymal vessels causes degeneration and necrosis of smooth muscle cells and leads to multiple cortical hemorrhages. Smooth muscle cells isolated from blood vessels with amyloid deposits secrete A beta and accumulate nonfibrillar A beta intracellularly. The amyloidogenic processing of APP can be enhanced by apolipoprotein E, reduced by transthyretin, and modulated by several cytokines.
Wisniewski
H M
HM
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Wegiel
J
J
Vorbrodt
A W
AW
Mazur-Kolecka
B
B
Frackowiak
J
J
D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000686:Amyloidosis / Q000473:pathology* / Q000503:physiopathology; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*
D016564:Amyloid beta-Protein Precursor