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.
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: P M Abdul Muneer; Saleena Alikunju; Adam M Szlachetka; James Haorah Journal: Arterioscler Thromb Vasc Biol Date: 2012-03-08 Impact factor: 8.311
Authors: M T Gentile; M G Reccia; P P Sorrentino; E Vitale; G Sorrentino; A A Puca; L Colucci-D'Amato Journal: Mol Neurobiol Date: 2012-05-31 Impact factor: 5.590
Authors: Katharina Schindowski; Anne Eckert; Jürgen Peters; Corinna Gorriz; Uta Schramm; Thomas Weinandi; Konrad Maurer; Lutz Frölich; Walter E Müller Journal: Neuromolecular Med Date: 2007-10-26 Impact factor: 3.843
Authors: Rongzhen Zhang; Robert G Miller; Catherine Madison; Xia Jin; Ronald Honrada; Will Harris; Jonathan Katz; Dallas A Forshew; Michael S McGrath Journal: J Neuroimmunol Date: 2013-02-04 Impact factor: 3.478