Distribution of the Iron-Binding Protein Lactoferrin in the Pathological Lesions of Neurodegenerative Diseases

Summary

In the present study, we analyzed the distribution of lactoferrin by immunohistochemistry in the cerebral cortex of patients presenting with Alzheimer’s disease (AD), Down’s syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC), sporadic ALS, or Pick’s disease. The results show that lactoferrin accumulates in the typical lesions of each pathologic condition investigated. For instance, in AD and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation (up to 100 and 180/mm², respectively) and inferior temporal cortex (up to 20 and 120/mm², respectively). Senile plaques and Pick bodies were also consistently labeled. These staining patterns were comparable to those obtained with antibodies to the microtubule-associated protein tau and to amyloid ßA4 protein, although fewer neurofibrillary tangles were positive for lactoferrin than for tau protein in neocortical areas. Neuronal cytoplasmic staining was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer’s disease, Guamanian cases, Pick’s disease, and particularly in Down’s syndrome. Lactoferrin was also strongly associated with Betz cells and motoneurons in the primary motor cortex, and these same lactoferrin-immunoreactive motoneurons were severely affected in the cases with ALS. The upregulation and the cellular distribution of lactoferrin observed in these neurodegenerative disorders may be key factors in the mechanisms of iron and aluminum transport and delivery into neurons potentially more vulnerable to the degenerative process. Through this specific mechanism, iron and aluminum may accumulate within select neuron populations and exert cytotoxic effects, which may result in the formation of intracellular lesions and neuronal death.