Related Experiment Videos
Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia
I Grundke-Iqbal1, J Fleming, Y C Tung
1New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Abstract:
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.
Insights
Ferritin accumulation in microglia is prominent in Alzheimer's disease plaques. This iron-storage protein may contribute to amyloid formation or its clearance by reactive microglia.
Area of Science:
- Neuroscience
- Neuropathology
- Immunology
Background:
- Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles.
- The role of iron metabolism and microglial activation in AD pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the presence and localization of ferritin in Alzheimer's disease brain tissue.
- To explore the relationship between ferritin, microglia, and AD pathology.
Main Methods:
- Immunohistochemistry was used to detect ferritin and HLA-DR (a marker for reactive microglia) in AD hippocampus.
- Western blot analysis was performed on isolated paired helical filaments.
Main Results:
- Strong ferritin immunoreactivity was found in neuritic plaques, primarily associated with proliferated, HLA-DR-positive microglia.
- Ferritin-positive microglia in diffuse plaques appeared normal.
- Extracellular neurofibrillary tangles, but not paired helical filaments, showed ferritin positivity.
- No correlation was observed between ferritin/microglia activity and blood-brain barrier leakage.
Conclusions:
- Ferritin accumulation in microglia is a significant feature of neuritic plaques in Alzheimer's disease.
- Ferritin may play a role in amyloid formation via free radical generation or in amyloid clearance by microglia.