Cells of monocyte/microglial lineage are involved in both microvessel amyloidosis and fibrillar plaque formation in APPsw tg mice.
Ultrastructural three-dimensional reconstruction indicates that deposition of amyloid in the wall of capillaries and in perivascular plaques in APP(SW) transgenic mice (Tg2576) represents two steps of one pathological process associated with inflammation of the vascular wall and perivascular space with cells of monocyte/microglia lineage and fibrillar amyloid-beta deposition. Plaque growth is associated with an increase in the number of microglial cells from two in the smallest plaque to 113 in the largest plaque; however, the growth in the number of microglial cells does not result in amyloid deposit degradation. On the contrary, an increase in the number and volume of microglial cells correlates with the growth of amyloid star from 62 to 34,460 microm(3), and an increase of the plaque volume from 1555 to 284,497 microm(3) (r=0.9). Growth in the number of microglial cells in the absence of morphological evidence of fibrillar amyloid internalization and phagocytosis indicates that microglial cells do not remove amyloid in Tg2576 mice. The study suggests that (a) the mechanism of capillary amyloidosis and plaque formation is similar, (b) the cells of monocyte/macrophage lineage play a critical role in fibrillar amyloid deposition in both types of lesions, and (c) treatment of one of these two forms of brain amyloidosis may affect both types of pathological changes.
Wegiel
Jerzy
J
Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. j_wegiel@msn.com
Imaki
Humi
H
Wang
Kuo-Chiang
KC
Wegiel
Jarek
J
Rubenstein
Richard
R
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology* / Q000648:ultrastructure; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D021621:Imaging, Three-Dimensional / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure
D016564:Amyloid beta-Protein Precursor