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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Beard, J. L., Connor, J. R., and Jones, B. C. (1993) Iron in the brain. Nutrition Rev. 51, 157–170.
Bouras, C., Hof, P. R., Giannakopoulos, P., Michel, J. P., and Morrison, J. H. (1994) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb. Cortex 4, 138–150.
de Souza, M. and Brock, J. H. (1989) Iron in Immunity, Cancer and Inflammation. Wiley, New York.
Faucheaux, B. A., Nillesse, N., Damier, P., Spik, G., Mouatt-Prigent, A., Pierce, A., Leveugle, B., Kubis, N., Hauw, J.-J., Agid, Y., and Hirsch, E. C. (1995) Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease. Proc. Natl. Acad. Sci. USA 92, 9603–9607.
Gutteridge, J. M. C. (1992) Iron and oxygen radicals in brain. Ann. Neurol. 32, S16–S21.
Hof, P. R., Perl, D. P., Loerzel, A. J., and Morrison, J. H. (1991) Neurofibrillary tangle distribution in the cerebral cortex of parkinsonism-dementia cases from Guam: differences with Alzheimer’s disease. Brain Res. 564, 306–313.
Hof, P. R., Bierer, L. M., Perl, D. P., Delacourte, A., Buée, L., Bouras, C., and Morrison, J. H. (1992) Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia. Regional and laminar distribution of neurofibrillary tangles and senile plaques. Arch. Neurol. 49, 946–953.
Kawamata, T., Tooyama, I., Yamada, T., Walker, D. G., and McGeer, P. L. (1993) Lactoferrin immunocytochemistry in Alzheimer and normal human brain. Am. J. Pathol. 142, 1574–1585.
Leveugle, B., Spik, G., Perl, D. P., Bouras, C., Fillit, H. M., and Hof, P. R. (1994) The iron-binding protein lactoferrin is present in pathologic lesions in a variety of neurodegenerative disorders: a comparative immunohistochemical analysis. Brain Res. 650, 20–31.
Osmand, A. P. and Switzer, R. C., III (1991) Differential distribution of lactoferrin and ALZ-50 immunoreactivities in neuritic plaques and neurofibrillary tangles in Alzheimer’s disease, in Alzheimer’s Disease: Basic Mechanisms, Diagnosis and Therapeutic Strategies (Iqbal, K., McLachlan, D. R. C., Winblad, B., and Wisniewski, H. M., eds.), Wiley, New York, pp. 219–228.
Yehuda, S. and Youdim, M. B. H. (1988) Brain Iron: Neurochemical and Behavioural Aspects. Taylor and Francis, London.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Humana Press Inc.
About this chapter
Cite this chapter
Leveugle, B., Spik, G., Perl, D.P., Bouras, C., Fillit, H.M., Hof, P.R. (1997). Distribution of the Iron-Binding Protein Lactoferrin in the Pathological Lesions of Neurodegenerative Diseases. In: Hutchens, T.W., Lönnerdal, B. (eds) Lactoferrin. Experimental Biology and Medicine, vol 28. Humana Press. https://doi.org/10.1007/978-1-4612-3956-7_8
Download citation
DOI: https://doi.org/10.1007/978-1-4612-3956-7_8
Publisher Name: Humana Press
Print ISBN: 978-1-4612-8439-0
Online ISBN: 978-1-4612-3956-7
eBook Packages: Springer Book Archive