amyloid (senile, neuritic) plaque

Introduction

Microscopic foci of extracellular amyloid deposition observed in patients with Alzheimer's disease, resulting from deposition of A4 or beta-peptide A4[1-42]. They are most numerous in limbic cortex & association cortex.

* see figure

Classification

Two types of plaques have been described.

• neuritic plaques (10 to > 120 um in diameter)
  • amyloid core (thioflavin & Congo-red positive)
  • dystrophic neurites
    • occur both within & immediately surrounding amyloid deposits
    • often dilated & tortuous
    • marked ultrastructural abnormalities
      • enlarged lysosomes
      • numerous mitochondria
  • paired helical filaments
  • activated microglia
  • reactive astrocytes
    • often ring the outside of the plaque
    • processes may extend toward central amyloid core
  • local inflammatory response
    • acute-phase proteins
    • cytokines
    • complement components
    • proteases
• diffuse plaques
  • diffuse deposits of amyloid
    • A4/42 is 1st component to appear in amyloid deposits
    • A4/40 precipitates on pre-existing A4/42 deposits
  • no dystrophic neurites
  • no associated reactive microglia
  • no inflammatory response
  • observed in association & limbic cortex, cerebellum, thalamus & striatum
  • may NOT stain with thioflavin & Congo-red stains
  • may be immature amyloid plaques
  • may be envisioned as dynamic structures with active A4 deposition & dissolution

Epidemiology

• air pollution associated with increased risk

Components:

• inorganic aluminosilicate*
• A4 or beta-protein*
  • diffuse plaques contain A4/42 alone
  • neuritic plaques contain both A4/40 & A4/42
  • amino terminal truncated forms of A4/42 (3-42, 4-42, 5-42, 8-42 & 9-42) identified as major constituents
• alpha-1 antichymotrypsin
• amyloid P component
• apolipoprotein E
• ICAM-1
• non A-beta component of AD amyloid
• butyrylcholinesterase
• diffuse amyloid deposits may contain GM1 ganglioside

* the core of senile plaques has two major components, inorganic aluminosilicate & A4 or beta-protein. Formation:

• may be formed by lysis of neurons & astrocytes containing A4/42
• neuritic plaques thought to develop over months to years
• plaques may form (& be cleared) rapidly in a mouse model

Inhibitors of ACAT1 enhance beta peptide & amyloid plaque removal in a mouse model for Alzheimer's disease

Laboratory

• amyloid in brain by light microscopy

More general terms

• abnormal morphologic structure (malformation)

Database

• OMIM: https://mirror.omim.org/entry/269800