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

Date Published:
05/2002

Publication Type:
Journal Article

Authors:

M. Fiala

Q.N. Liu

J.W. Sayre

V. Pop

V. Brahmandam

M.C. Graves

H.V. Vinters

Secondary:
European Journal of Clinical Investigation

Volume:
32

Pagination:
360-71

Issue:
5

URL:
https://pubmed.ncbi.nlm.nih.gov/

Keywords:
80 and over;Aged;Alzheimer Disease;Amyloid beta-Protein;Antigens;CD;Cerebrovascular Circulation;Cyclooxygenase 2;Differentiation;External;Isoenzymes;Myelomonocytic;Peptide Fragments;Prostaglandin-Endoperoxide Synthases

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.