Summary
Nuclear and chromatin fractions were prepared from cerebral cortex of 34 human and 37 animal brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Compared to age-matched controls, aluminum content expressed per gram of DNA was significantly increased in nuclear and heterochromatin fractions in pre-senile Alzheimer's disease. In contrast nuclear preparations from brains of patients who had died with dialysis encephalopathy contained less aluminum than controls, although whole tissue concentrations were elevated ten to fifteen times above the control concentrations.
Direct injection of aluminum into the cerebrospinal fluid of cats resulted in a progressive encephalopathy with neurofibrillary degeneration and increased intranuclear aluminum content. It is speculated that in Alzheimer's disease the normal blood-brain and cytoplasmic barriers for this neurotoxic metal are defective permitting aluminum to gain access to DNA-containing constitutents of the nuclei.
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References
Alfrey AC, Le Gendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome: possible aluminum intoxication. N Engl J Med 294:184–188
Arieff AI, Cooper JD, Armstrong D, Lazaromitz BS (1979) Dementia, renal failure, and brain aluminum. Ann Intern Med 90:741–747
Bryan SE, Simons SJ, Vizard DL, Hardy KJ (1976) Interactions of mercury and copper with constitutive heterochromatin and euchromatin in vivo and in vitro. Biochemistry 15:1667–1671
Crapper DR (1973) Experimental neurofibrillary degeneration and altered electrical activity. Electroencephalogr Clin Neurophysiol 35:575–588
Crapper DR, Dalton AJ (1973) Alterations in short-term retention, conditioned avoidance response acquisition and motivation following aluminum induced neurofibrillary degeneration. Physiol Behav 10:925–933
Crapper DR (1974) Dementia: Recent observations in Alzheimer's disease and experimental aluminum encephalopathy. In: Seeman P, Brown GM (eds) Frontiers in neurology and neuroscience research. University of Toronto Press, Toronto, pp 97–111
Crapper DR, Dalton AJ, Skopitz M, Scott JW, Hachinski VC (1975) Alzheimer degeneration in Down syndrome. Electrophysiologic alterations and histopathologic findings. Arch Neurol 3:618–623
Crapper DR, Krishnan SS, Quittkat S (1976) Aluminum, neurofibrillary degeneration, and Alzheimer's disease. Brain 99:67–80
Crapper DR, Karlik S, De Boni U (1978) Aluminum and other metals in senile (Alzheimer) dementia. In: Katzman R, Terry RD, Beck KL (eds) Alzheimer's disease, senile dementia, and related disorders, vol 7, Aging. Raven Press, New York, pp 471–485
Crapper DR, Quittkat S, De Boni U (1979) Altered chromatin conformation in Alzheimer's disease. Brain 102:483–495
De Boni U, Scott JW, Crapper DR (1974) Intracellular aluminum binding: a histochemical study. Histochemistry 40:31–37
De Boni U, Crapper DR (1978) Paired helical filaments of the Alzheimer type in cultured neurons. Nature 271:566–568
Finch JT, Klug A (1976) Solenoidal model for super-structure in chromatin. Proc Natl Acad Sci USA 73:1897–1901
Hardy KJ, Bryan SE (1975) Localization and uptake of copper into chromatin. Toxicol Appl Pharmacol 33:62–69
Kidd M (1964) Alzheimer's disease, an electron microscopical study. Brain 87:308–319
King GA, De Boni U, Crapper DR (1975) Effect of aluminum upon conditioned avoidance response acquisition in the absence of neurofibrillary degeneration. Pharmacol Biochem Behav 3:1003–1009
Klatzo I, Wisiniewski H, Streicher E (1965) Experimental production of neurofibrillary degeneration. J Neuropathol Exp Neurol 24:187–199
Krishnan SS, Quittkat S, Crapper DR (1976) Atomic absorption analysis for traces of aluminum and vanadium in biological tissue. A critical evaluation of the graphite furnace atomizer. Can J Spectrosc 21:25–30
Kushelevsky A, Yagil R, Alfosi Z, Berlyne GM (1976) Uptake of aluminum ion by the liver. Biomedicine 25:59–60
Leake RE, Trench ME, Barry JM (1972) Effect of cations in the condensation of hen erythrocyte nuclei and its relation to gene activation. Exp Cell Res 71:17–26
Matsuyama H, Nakamura S (1978) Senile changes in the brain in the Japanese: incidence of Alzheimer's neurofibrillary change and senile plaques. In: Katzman R, Terry RD, Beck KL (eds) Alzheimer's disease: senile dementia and realed disorders, vol 7, Aging. Raven Press, New York, pp 287–297
Mayor GH, Keiser JA, Makdoni D, Ku P (1977) Aluminum absorption and distribution: effect of parathyroid hormone. Science 197:1187–1189
McDermott JR, Smith AI, Iqbal K, Wisniewski HM (1977) Aluminum and Alzheimer's disease. Lancet II:710–711
McDermott JR, Smith AI, Ward MK, Parkinson IS, Kerr D (1978) Brain — aluminum concentration in dialysis encephalopathy. Lancet I:901–904
Perl DP, Brody AR (1979) Detection of focal accumulations of aluminum (Al) and silicon (Si) with neurofibrillary tangle bearing neurons of Alzheimer's disease. J Neuropathol Exp Neurol 38:335 (Abstract 102)
Robinson N (1966) Composition of deoxyribonucleoprotein in human brain. Clin Chim Acta 14:429–434
Ryan T, Potter HD (1978) A Mg2+ dependent class of thick filaments and correlated nuclear chromatin in cat-fish photoreceptors. J Neurocytol 7:313–321
Terry RD, Gonatas NK, Weiss M (1964) Ultrastructural studies in Alzheimer's pre-senile dementia. Am J Pathol 44:269–297
Terry RD, Pena C (1965) Experimental production of neurofibrillary degeneration. Electron microscopy, phosphatase histochemistry and electron-probe analysis. J Neuropathol Exp Neurol 24:200–210
Trapp GA, Miner GD, Zimmerman RL, Mastri RA, Heston LL (1978) Aluminum levels in brain in Alzheimer disease. Biol Psychol 13:709–718
Thoma F, Koller TH (1978) The ionic strength dependence of chromatin folding. In: Sturgess JM (ed) Electronmicroscopy, vol II, Biology. Ninth International Congress on Electron microscopy. The Microscopical Society of Canada, Toronto, pp 220–221
Yase Y (1977) The basic process of amyotrophic lateral sclerosis as reflected in Kii peninsula and Guam. Excerpt Med Internat Cong Series 434. Neurology 43:413–427
Yase Y (1978) Kii peninsula amyotrophic lateral sclerosis. USPHS, NIW CS, NJH Guam Alz/PD Workshop
Yoshimasu F, Uebayaski Y, Yase Y, Iwata S, Sasajima K (1976) Studies on amytrophic lateral sclerosis by neutron activation analysis. Folia Psychiatr Neurol Jpn 30:49–55
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Crapper, D.R., Quittkat, S., Krishnan, S.S. et al. Intranuclear aluminum content in Alzheimer's disease, dialysis encephalopathy, and experimental aluminum encephalopathy. Acta Neuropathol 50, 19–24 (1980). https://doi.org/10.1007/BF00688530
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DOI: https://doi.org/10.1007/BF00688530