Neuritic plaque evolution in Alzheimer’s disease is accompanied by transition of activated microglia from primed to enlarged to phagocytic forms |
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| Authors: | J. G. Sheng Robert E. Mrak W. Sue T. Griffin |
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| Affiliation: | (1) Department of Veterans’ Affairs Medical Center, Little Rock, AR 72 205, USA, US;(2) Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72 205, USA, US;(3) Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72 205, USA, US;(4) Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, AR 72 205, USA, US;(5) Department of Neurology, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai, 200 025, China, CN;(6) Geriatric Research, Education and Clinical Center, John L. McClellan Memorial Veterans’ Hospital, 4300 West 7th Street, Little Rock, AR 72 205, USA Tel.: 1-501-660-2069; Fax; 1-501-671-2524, US |
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| Abstract: | Activated microglia, overexpressing the potent neuroactive cytokine interleukin-1, have been implicated as a driving force in the evolution of diffuse amyloid deposits into diagnostic neuritic plaques in Alzheimer’s disease. To evaluate this role further, we used double-label immunohistochemistry to classify and quantify plaque-associated and non-plaque-associated activated interleukin-1-immunoreactive microglia in parahippocampal tissue from 11 patients with Alzheimer’s disease. These activated microglia were subclassified as primed (only slightly enlarged), enlarged, or phagocytic (enlarged with heterogeneous cytoplasmic contents). We further determined the distribution of these microglial subtypes among four defined plaque types. Most (84%) primed microglia were not plaque associated, although 13% were present in diffuse non-neuritic plaques and 3% were present in diffuse neuritic plaques. In contrast, most enlarged (55%) and phagocytic (91%) microglia were plaque associated. Of plaque-associated enlarged microglia, most (71%) were found in diffuse neuritic plaques with the remainder evenly distributed between diffuse non-neuritic and dense-core neuritic plaques (15% each). Of plaque-associated phagocytic microglia, a few were present in diffuse non-neuritic plaques (5%), but most were found in diffuse neuritic plaques (62%) and dense-core neuritic plaques (33%). These findings show preferential association of primed microglia with diffuse amyloid deposits and imply that microglial transformation from primed, to enlarged, to phagocytic types occurs in concert with the evolution of amyloid plaques from diffuse amyloid deposits to the neuritic β-amyloid plaque forms in Alzheimer’s disease. Microglial phagocytic activity in neuritic plaques may reflect involvement in the processing of diffuse amyloid into condensed β-amyloid, or in clearance of neuritic debris. Received: 15 January 1997 / Accepted: 17 March 1997 |
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| Keywords: | Alzheimer’ s disease β -Amyloid Inflammation Microglia Neuritic plaque |
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