Acta Neuropathologica

, Volume 100, Issue 4, pp 356–364

Microglial cells are the driving force in fibrillar plaque formation, whereas astrocytes are a leading factor in plaque degradation

  • J. Wegiel
  • K. -C. Wang
  • M. Tarnawski
  • B. Lach
Regular paper

DOI: 10.1007/s004010000199

Cite this article as:
Wegiel, J., Wang, KC., Tarnawski, M. et al. Acta Neuropathol (2000) 100: 356. doi:10.1007/s004010000199

Abstract

Ultrastructural three-dimensional reconstruction of human classical plaques in different stages of development shows that microglial cells are the major factor driving plaque formation by fibrillar amyloid-β (Aβ) deposition. The amount of fibrillar Aβ released by microglial cells and the area of direct contact between amyloid and neuron determine the extent of dystrophic changes in neuronal processes and synapses. The volume of hypertrophic astrocytic processes separating fibrillar amyloid from neuron is a measure of the protective activation of astrocytes. On the bases of the volume of amyloid star, microglial cells, dystrophic neurites, and hypertrophic astrocytic processes, and spatial relationships between plaque components, three stages in classical plaque development have been distinguished: early, mature, and late. In early plaque, the leading pathology is fibrillar Aβ deposition by microglial cells with amyloid star formation. The mature plaque is characterized by a balance between amyloid production, neuronal dystrophy, and astrocyte hypertrophy. In late classical plaque, microglial cells retract and expose neuropil on direct contact with amyloid star, enhancing both dystrophic changes in neurons and hypertrophic changes in astrocytes. In late plaques, activation of astrocytes predominates. They degrade amyloid star and peripheral amyloid wisps. The effect of these changes is classical plaque degradation to fibrillar primitive and finally to nonfibrillar, diffuse-like plaques.

Key words Alzheimer disease Fibrillar amyloid-β Astrocytes Microglial cell Ultrastructure 

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • J. Wegiel
    • 1
  • K. -C. Wang
    • 1
  • M. Tarnawski
    • 1
  • B. Lach
    • 2
  1. 1.Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA e-mail: J_Wegiel@email.msn.com, Tel.: +1-718-4945231, Fax: +1-718-9826346US
  2. 2.Laboratory Medicine, Ottawa Civic Hospital, Ottawa, Ontario, CanadaCA

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