Distribution of interleukin-1-immunoreactive microglia in cerebral cortical layers: implications for neuritic plaque formation in Alzheimer's disease.
Activated microglia overexpressing interleukin-1 (IL-1) are prominent neuropathological features of Alzheimer's disease. We used computerized image analysis to determine the number of IL-1 alpha-immunoreactive (IL-1 alpha +) microglia in cytoarchitectonic layers of parahippocampal gyrus (Brodmann's area 28) of Alzheimer and control patients. For cortical layers I and II, the numbers of IL-1 alpha + microglia were similar in Alzheimer and control patients. For layers III-VI, the numbers of IL-1 alpha + microglia were higher than that seen in layers I-II for both Alzheimer and control patients. Moreover, for layers III-VI, the number of IL-1 alpha + microglia in Alzheimer patients was significantly greater than that in control patients (relative Alzheimer values of threefold for layer III-V and twofold for layer VI; P < 0.05 in each case). The cortical laminar distribution of IL-1 alpha + microglia in Alzheimer patients correlated with the cortical laminar distribution of beta-amyloid precursor protein-immunoreactive (beta-APP+) neuritic plaques found in Alzheimer patients (r = 0.99, P < 0.005). Moreover, the cortical laminar distribution of IL-1 alpha + microglia in control patients also correlated with the cortical laminar distribution of beta-APP+ neuritic plaques found in Alzheimer patients (r = 0.91, P < 0.05). These correlations suggest that pre-existing laminar distribution patterns of IL-1 alpha + microglia (i.e. that seen in control patients) are important in determining the observed laminar distribution of beta-APP+ neuritic plaques in Alzheimer patients. These findings provide further support for our hypothesis that IL-1 is a key driving force in neuritic plaque formation in Alzheimer's disease.
Geriatric Research, Education and Clinical Center, University of Arkansas for Medical Sciences, Little Rock, USA.
J G
JG
Sheng
W S
WS
Griffin
M C
MC
Royston
R E
RE
Mrak
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000276:immunology; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis* / Q000276:immunology; D008297:Male; D017628:Microglia / Q000737:chemistry*; D058225:Plaque, Amyloid / Q000737:chemistry*; D013702:Temporal Lobe / Q000737:chemistry / Q000166:cytology
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1