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Migration of perivascular cells into the neuropil and their involvement in beta-amyloid plaque formation
1Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Abstract:
Our recent ultrastructural studies of amyloid angiopathy in biopsy specimens from Alzheimer's disease patients showed that perivascular cells and perivascular microglia are involved in the production of amyloid fibrils. Further examination of the walls of the vessels with and without amyloid deposits presented in this report reveals numerous mononuclear cells with a broad spectrum of morphological appearances. Some of these cells produce amyloid in the vascular wall and migrate into the neuropil. Others do not produce amyloid in this location but also migrate through the vascular basal lamina and position themselves on the external surface of basal lamina or in the neuropil outside the vascular astrocytic end-feet processes. The presence of clusters or rows of six or more of these cells in the position of perivascular microglial cells suggests their proliferation in the perivascular region. After leaving the perimeter of the vessel wall, perivascular cells become the perivascular, neuropil, and satellite microglia cells. Migrating perivascular cells become the microglia, which are engaged in amyloid fibril formation and development of classical and primitive plaques.
Insights
Perivascular cells and microglia in Alzheimer's disease (AD) produce amyloid fibrils. These cells migrate from vessel walls, becoming microglia involved in plaque formation.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Alzheimer's disease (AD) is characterized by amyloid angiopathy and plaque formation.
- The cellular origins of amyloid fibril production in the brain vasculature remain incompletely understood.
Purpose of the Study:
- To investigate the role of perivascular cells and microglia in amyloid fibril production within the vascular walls of Alzheimer's disease patients.
- To characterize the migration and differentiation of these cells in the brain.
Main Methods:
- Ultrastructural analysis of biopsy specimens from Alzheimer's disease patients.
- Morphological examination of mononuclear cells within and around cerebral blood vessels.
Main Results:
- Perivascular cells and microglia were identified as producers of amyloid fibrils in the vascular walls.
- Mononuclear cells exhibited diverse morphologies, with some producing amyloid and migrating into the neuropil.
- Cellular proliferation was observed in the perivascular region, suggesting perivascular microglia expansion.
- Migrating perivascular cells differentiate into various microglial subtypes (perivascular, neuropil, satellite).
Conclusions:
- Perivascular cells and microglia are key players in amyloid angiopathy and amyloid fibril formation in Alzheimer's disease.
- These cells actively migrate and proliferate, contributing to the development of amyloid plaques in the brain parenchyma.