Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier.

Abstract

BACKGROUND:

Monocyte/macrophages are known to infiltrate the brain of patients with HIV-1 encephalitis (HIVE). In Alzheimer's disease brain, the origin of activated microglia has not been determined.

MATERIALS AND METHODS:

We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid-beta plaques and the blood-brain barrier in autopsy brain tissues from patients with Alzheimer's disease (AD) and HIVE.

RESULTS:

In both conditions, cyclooxygenase-2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO-1 disruption. The macrophages also infiltrate amyloid-beta plaques, display intracellular amyloid-beta and are surrounded by amyloid-beta-free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid-beta-containing vessels in amyloid angiopathy, and exhibit intracellular amyloid-beta but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0.034), and AD tissues have significantly greater leakage than control tissues (P = 0.0339). The AD group differs from a normal control age-matched group with respect to both the area occupied by CD68 (P = 0.03) and cyclooxygenase-2 immunoreactive cells (P = 0.004).

CONCLUSION:

In both HIVE and AD, blood-borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood-brain barrier. The lacunae around macrophages in amyloid-beta plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid-beta deposits in vitro.

• Authors: M Fiala, Q N Liu, J Sayre, V Pop, V Brahmandam, M C Graves, H V Vinters
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 32 Issue 5 Pg. 360-71 (May 2002) ISSN: 0014-2972 [Print] England
• PMID: 12027877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amyloid beta-Peptides
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 antigen, human
• Isoenzymes
• Membrane Proteins
• Peptide Fragments
• amyloid beta-protein (1-34)
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• AIDS Dementia Complex (immunology, metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease (immunology, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Antigens, CD (immunology, metabolism)
• Antigens, Differentiation, Myelomonocytic (immunology, metabolism)
• Blood-Brain Barrier
• Brain (metabolism, pathology)
• Cerebrovascular Circulation
• Cyclooxygenase 2
• HIV-1
• Humans
• Immunohistochemistry
• Isoenzymes (metabolism)
• Lymphocytes (physiology)
• Macrophages (physiology)
• Male
• Membrane Proteins
• Middle Aged
• Peptide Fragments (metabolism)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Tight Junctions (metabolism)