DISTRIBUTION OF INTERLEUKIN-1-IMMUNOREACTIVE MICROGLIA IN CEREBRAL CORTICAL LAYERS - IMPLICATIONS FOR NEURITIC PLAQUE-FORMATION IN ALZHEIMERS-DISEASE

Activated microglia overexpressing interleukin-1 (IL-1) are prominent neuropathological features of Alzheimer's disease. We used computerize d image analysis to determine the number of IL-1 alpha-immunoreactive (IL-1 alpha(+)) microglia in cytoarchitectonic layers of parahippocamp al gyrus (Brodmann's area 28) of Alzheimer and control patients, For c ortical layers I and II, the numbers of IL-1 alpha(+) microglia were s imilar in Alzheimer and control patients, For layers III-VI, the numbe rs of IL-1 alpha(+) microglia were higher than that seen in layers I-I I for both Alzheimer and control patients, Moreover, for layers III-VI , the number of IL-1 alpha(+) microglia in Alzheimer patients was sign ificantly greater than that: in control patients (relative Alzheimer v alues 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(+) micr oglia in Alzheimer patients correlated with the cortical laminar distr ibution of beta-amyloid precursor protein-immunoreactive (beta-APP(+)) neuritic plaques found in Alzheimer patients (r = 0.99, P < 0.005), M oreover, the cortical laminar distribution of IL-1 alpha(+) microglia in control patients also correlated with the cortical laminar distribu tion 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 co ntrol patients) are important in determining the observed laminar dist ribution 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.