Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia

Summary A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus. The ferritin accumulation was almost exclusively associated with the microglia, which appeared to have proliferated greatly. These cells were also positive for HLA-DR, a putative marker for reactive microglia. In contrast, in the diffuse plaques, which were without neuritic pathology, the ferritin-stained microglia appeared to be normal. Microglia were seen frequently in contact with neurons undergoing neurofibrillary changes but only the tangles in the extracellular space were ferritin positive. No ferritin was detected, by Western blots, in paired helical filaments isolated from Alzheimer's disease brain, suggesting that ferritin was most likely weakly associated with and was not a constituent of these fibrils. No correlation between increased ferritin/microglia activity and blood-brain barrier leakage was detected. Ferritin, an iron-storage protein, might have a role in the formation of amyloid through the action of free radicals generated during the release of iron from the ferritin molecule. Alternatively, the ferritin/microglia system might be secondarily involved in the removal and processing of the amyloid.Supported in part by the New York State Office of Mental Retardation and Developmental Disabilities and National Institutes of Health grants NS18105, AG05892 and AG04220. H. L. was funded by a grant from the Ministry for Science and Research, Austria, J. G. J. and J. F. were funded by the Council for Tobacco Research. Parts of this paper have been reported at the 9th International Conference on Proteins of Iron Transport and Storage, Brisbane, Australia, June 1989 and at the 2nd International Conference on Aluminium and Health, Orlando, Fla, USA, December 1989