Abstract
Aluminum has been presumed to be involved in the pathogenesis or etiology of Alzheimer's disease. Histochemical demonstration of aluminum in autopsy brains from Alzheimer's disease victims by means of the solochrome azurine method in combination with the methenamine silver technique revealed aluminum-related staining in some neocortical and hippocampal senile plaques and tangles, as well as in the cytoplasm and/or the nuclei of some neurons, and in the cytoplasm of endothelial cells of blood capillaries and pericytes around larger blood vessels. In double-stained samples (first with methenamine silver and then with solochrome azurine) only some plaques displayed the presence of aluminum, while others did not show any sign of the presence of the trace metal. The specificity and sensitivity of solochrome azurine staining was checked in paper spot-test and test-tube experiments combined with flameless atomic absorption spectrophotometry. The results suggest that aluminum is present in brain samples from Alzheimer's disease victims, but the structural localization indicates that it is not primarily involved in the etiology of the disease.
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Alfrey AC, LeGendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med 294:184–188
Buchanan MRC, Ihle BU, Dunn CM (1981) Haemodialysis related osteomalacia: a staining method to demonstrate aluminium. J Clin Pathol 34:1352–1354
Candy JM, Edwardson JA, Klinowski J, Oakley AE, Perry EK, Perry RH (1985) Colocalization of aluminium and silicon in senile plaques: implications for the neurochemical pathology of Alzheimer's disease. In: Traber J, Gispen WH (eds) Senile dementia of the Alzheimer type. Springer, Berlin Heidelberg New York, pp 183–197
Candy JM, Klinowski J, Perry RH, Perry EK, Fairbairn A, Oakley AE, Carpenter TA, Atack JR, Blessed G, Edwardson JA (1986) Aluminosilicates and senile plaque formation in Alzheimer's disease. Lancet I:354–356
Chafi AH, Hauw J-J, Rancurel G, Berry J-P, Galle C (1991) Absence of aluminium in Alzheimer's disease brain tissue: electron microprobe and ion microprobe studies. Neurosci Lett 123:61–64
Clark RA, Krueger GL (1985) Aluminon: its limited application as a reagent for the detection of aluminum species. J Histochem Cytochem 33:729–732
Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science 180:511–513
Crapper DR, Krishnan SS, Quittkat S (1976) Aluminum, neurofibrillary degeneration and Alzheimer's disease. Brain 99: 67–80
Crapper DR, Quittkat S, Krishnan SS, Dalton AJ, De Boni U (1980) Intranuclear aluminum content in Alzheimer's disease, dialysis encephalopathy and experimental aluminum encephalopathy. Acta Neuropathol (Berl) 50:19–24
Crapper McLachlan DR (1986) Aluminum and Alzheimer's disease. Neurobiol Aging 7:525–532
Crapper McLachlan DR, Lukiw WJ, Kruck TPA (1989) New evidence for an active role of aluminum in Alzheimer's disease. Can J Neurol Sci 16:490–497
Denton J, Froemont AJ, Ball J (1984) Detection and distribution of aluminium in bone. J Clin Pathol 37:136–142
Duckett S, Galle P (1976) Mise en évidence de l'aluminum dans les plaques de la maladie d'Alzheimer: etudie à la microsonde de Castaing: C R Acad Sci [D] 282:393–395
Edwardson JA, Candy JM (1989) Aluminium and the pathogenesis of senile plaques in Alzheimer's disease, Down's syndrome and chronic renal dialysis. Ann Med 21:95–97
Edwardson JA, Candy JM, Ince PG, McArthur FK, Morris CM, Oakley AE, Taylor GA, Bjertness E (1992) Aluminium accumulation, β-amyloid deposition and neurofibrillary changes in the central nervous system. Ciba Found Symp 169:165–185
Ellis HA, Pang MMC, Mawhinney WHB, Skillen AW (1988) Demonstration of aluminium in iliac bone: correlation between aluminon and solochrome azurine staining techniques with data on flameless absorption spectrophotometry. J Clin Pathol 41: 1171–1175
Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann Neurol 31:286–292
Jacobs RW, Duong T, Jones RE, Trapp GA, Scheibel AB (1989) A reexamination of aluminum in Alzheimer's disease: analysis by energy dispersive X-ray microprobe and flameless atomic absorption spectrophotometry. Can J Neurol Sci 16:498–503
Kawahara M, Muramoto K, Kobayashi K, Mori H, Kuroda Y (1994) Aluminum promotes the aggregation of Alzheimer's amyloid β-protein in vitro. Biochem Biophys Res Commun 198:531–535
Khachaturian ZS (1985) Diagnosis of Alzheimer's disease. Arch Neurol 42:1097–1105
Landsberg JP, Mcdonald B, Watt F (1992) Absence of aluminium in neuritic plaque cores in Alzheimer's disease. Nature 360:65–68
Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RW, Beyreuther K (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same proteins the amyloid of plaque cores and blood vessel. EMBO J 4:2757–2763
McDermott JR, Smith AI, Iqbal K, Wisniewski HM (1979) Brain aluminum in aging and Alzheimer disease. Neurology 29: 809–814
McLachlan DR, Fraser PE, Dalton AJ (1992) Aluminium and the pathogenesis of Alzheimer's disease: a summary of evidence. Ciba Found Symp 169:87–108
Meiri H, Banin E, Roll M, Rousseau A (1993) Toxic effects of aluminium on nerve cells and synaptic transmission. Prog Neurobiol 40:89–121
Mori H, Swyt C, Smith QR, Atack JR, Rapoport SI (1988) In situ X-ray microanalysis of senile plaques in Alzheimer's disease. Neurology 38 [Suppl 1]:230
Murray FES, Landsberg JP, Williams RJP, Esiri MM, Watt F (1992) Elemental analysis of neurofibrillary tangles in Alzheimer's disease using proton-induced X-ray analysis. Ciba Found Symp 169:201–216
Nikaido T, Austin J, Rinehart R, Trueb L, Hutchinson J, Stukenbrok H, Miles B (1971) Studies in ageing of the brain. I. Isolation and preliminary characterization of Alzheimer plaques and cores. Arch Neurol 25:198–211
Perl PD, Brody AR (1980) Alzheimer disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208:297–299
Perl PD, Pendlebury WW (1986) Aluminum neurotoxicity-Potential role in the pathogenesis of neurofibrillary tangle formation. Can J Neurol Sci 13:441–445
Pettegrew JW (1986) Aluminum and Alzheimer's disease: an evolving understanding. Neurobiol Aging 7:539–540
Piccardo P, Yanagihara R, Garruto RM, Gibbs CJ Jr, Gajdusek DC (1988) Histochemical and X-ray microanalytical localization of aluminum in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Acta Neuropathol 77:1–4
Senitz D, Bluthner K (1990) The presence of aluminum in cerebral vessels in Alzheimer's disease. Zentralbl Allg Pathol 136:329–335
Szerdahelyi P, Kása P (1988) Intraventricular administration of the cholinotoxin AF64A increases the accumulation of aluminum in the rat parietal cortex and hippocampus, but not in the frontal cortex. Brain Res 444:356–360
Verbueken AH, Vyver FL van de, Visser WJ, Grieken RE van, Broe ME de (1986) Laser microprobe mass analysis (LAMMA) to verify the aluminon staining of bone. Stain Technol 61:287–294
Wisniewski HM (1990) About the association of aluminum and Alzheimer disease — A commentary. In: Nicolini M, Zatta PF, Corain B (eds) Aluminum in chemistry biology and medicine. Raven Press, New York, pp 115–117
Wisniewski HM, Wen GY (1992) Aluminium and Alzheimer's disease. Ciba Found Symp 169:142–164
Wisniewski HM, Moretz RC, Iqbal K (1986) No evidence for aluminum in etiology and pathogenesis of Alzheimer's disease. Neurobiol Aging 7:532–535
Yamaguchi H, Haga G, Hirai S, Nakazato Y, Kosaka K (1990) Distinctive, rapid, and easy labeling of diffuse plaques in the Alzheimer brains by a new methenamine silver stain. Acta Neuropathol 79:569–572
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Kasa, P., Szerdahelyi, P. & Wisniewski, H.M. Lack of topographical relationship between sites of aluminum deposition and senile plaques in the Alzheimer's disease brain. Acta Neuropathol 90, 526–531 (1995). https://doi.org/10.1007/BF00294815
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DOI: https://doi.org/10.1007/BF00294815