Glial reactions and the clearance of amyloid beta protein in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type

Acta Neuropathol. 2004 May;107(5):389-98. doi: 10.1007/s00401-004-0824-4. Epub 2004 Mar 10.

Abstract

Although the amyloid beta protein (Abeta) E693Q mutation enhances Abeta fibrillization in vitro and cerebral amyloid angiopathy (CAA) in vivo, brain parenchymal Abeta deposition and tau pathology in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) are limited. To evaluate whether clearance of Abeta by glial cells may play a role in this regard, this immunohistochemical study of frontal cortex of 14 HCHWA-D autopsy brains was performed using double staining with glial markers and end-specific antibodies to Abetax-42 (Abeta42) and Abetax-40 (Abeta40). Tau pathology was also assessed. Numerous microglia and/or astrocytes carrying cytoplasmic Abeta42(+)40(-) granules were scattered among non-fibrillar (Congo red-negative) Abeta deposits, i.e., clouds, fine diffuse plaques, and Abeta42(+)40(-) dense diffuse plaques. On the other hand, activated microglia and reactive astrocytes associated with fibrillar (Congo red-positive) Abeta deposition, i.e., Abeta42(+)40(+) dense diffuse plaques and CAA invading the parenchyma, were virtually devoid of Abeta granules. Tau pathology was scant and most frequently associated with CAA. These results suggest that relatively non-fibrillar parenchymal Abeta deposits may be liable to glial clearance. Abeta sequestration by glial cells may be a factor limiting the levels of neurotoxic soluble Abeta oligomers in HCHWA-D brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cerebral Amyloid Angiopathy
  • Cerebral Amyloid Angiopathy, Familial* / complications
  • Cerebral Amyloid Angiopathy, Familial* / metabolism
  • Cerebral Amyloid Angiopathy, Familial* / pathology
  • Cerebral Hemorrhage* / complications
  • Cerebral Hemorrhage* / metabolism
  • Cerebral Hemorrhage* / pathology
  • Female
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glucose Transporter Type 5
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Monosaccharide Transport Proteins / metabolism
  • Neuroglia / classification
  • Neuroglia / pathology*
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / metabolism
  • Postmortem Changes
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Glial Fibrillary Acidic Protein
  • Glucose Transporter Type 5
  • Monosaccharide Transport Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins