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-1α-immunoreactive (IL-1α + ) 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-1α + microglia were similar in Alzheimer and control patients. For layers III-VI, the numbers of IL-1α + 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-1α + 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-1α + microglia in Alzheimer patients correlated with the cortical laminar distribution of β-amyloid precursor protein-immunoreactive (β-APP + ) neuritic plaques found in Alzheimer patients (r=0.99, P<0.005). Moreover, the cortical laminar distribution of IL-1α + microglia in control patients also correlated with the cortical laminar distribution of β-APP + neuritic plaques found in Alzheimer patients (r=0.91, P<0.05). These correlations suggest that pre-existing laminar distribution patterns of IL-1α + microglia (i.e. that seen in control patients) are important in determining the observed laminar distribution of β-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.