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Aluminum Neurotoxicity — Potential Role in the Pathogenesis of Neurofibrillary Tangle Formation

  • Daniel P. Perl (a1) and William W. Pendlebury (a1)

Abstract:

Alzheimer's disease is a progressive neurodegenerative disease characterized neuropathologically by the development of large numbers of neurofibrillary tangles in certain neuronal populations of affected brains. This paper presents a review of the available evidence which suggests that aluminum is associated with Alzheimer's disease and specifically with the development of the neurofibrillary tangle. Aluminum salts innoculated into experimental animals produce neurofilamentous lesions which are similar, though not identical, to the neurofibrillary tangle of man. Although a few reports have suggested evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Using scanning electron microscopy with x-ray spectrometry, we have identified accumulations of aluminum in neurofibrillary tangle-bearing neurons of Alzheimer's disease. Similar accumulations have been identified in the neurofibrillary tangle-bearing neurons found in the brains of indigenous natives of Guam who suffer from parkinsonism with dementia and amyotrophic lateral sclerosis. This ongoing research still cannot ascribe a causal role of aluminum in the pathogenesis of neurofibrillary tangle formation; however, it does suggest that environmental factors may play an important part in the formation of this abnormality.

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Copyright

Corresponding author

Neuropathology Division, Mount Sinai Medical Center, One Gustave Levy Place, New York, NY USA 10029

References

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1.Alzheimer, A.Ueber eine eigenartige Erkrankung der Hirnrinde. Allgemeine Z Psychiartr 1907; 64: 146148.
2.Corsellis, JNN.Aging and the dementias. In: Adams, JH, Corsellis, JAN, Duchen, LW, eds. Greenfield’s Neuropathology, 4th ed. New York: John Wiley, 1984: pp. 9511025.
3.Tomlinson, BE, Blessed, G, Roth, M.Observations on the brains of demented old people. J Neurol Sci 1970; 2: 205242.
4.Tomlinson, BE, Blessed, G, Roth, M.Observations on the brains of nondemented old people. J Neurol Sci 1968; 7: 331356.
5.Dayan, AD.Quantitative histological studies on the aged human brain. 1. Senile plaques and neurofibrillary tangles in “normal” people. Acta Neuropath 1970; 16: 8594.
6.Klatzo, I, Wisniewski, H, Streicher, E.Experimental production of neurofibrillary degeneration. 1. Light microscopic observations. J Neuropath Exptl Neurol 1965; 24: 187199.
7.Terry, RD, Pena, C.Experimental production of neurofibrillary degeneration. 2. Electron microscopy, phosphatase histochemistry and electron probe analysis. J Neuropath Exptl Neurol 1965; 24: 200210.
8.Wisniewski, HM, Narkewica, O, Wisniewski, K.Topography and dynamics of neurofibrillary degeneration in aluminum encephalopathy. Acta Neuropathol 1967; 9: 172133.
9.Crapper, DR, Dalton, AJ.Alterations in short-term retention, conditioned avoidance response, acquisition and motivation following aluminum induced neurofibrillary degeneration. Physiol Behav 1973; 10: 925933.
10.Terry, RD.Electron microscopic studies of Alzheimer’s disease and of experimental neurofibrillary tangles. In: Bailey, OT, Smith, DE, eds. The Central Nervous System. Baltimore, Williams & Wilkins, 1968: 213224.
11.Kidd, M.Paired helical filaments in electron microscopy of Alzheimer’s disease. Nature 1963; 197: 192193.
12.Wisniewski, HM, Narang, HK, Terry, RD.Neurofibrillary tangles of paired helical filaments. J Neurol Sci 1976; 27: 173181.
13.Selkoe, DJ, Ihara, Y, Salazar, FJ.Alzheimer’s disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Science 1982; 215: 12431245.
14.Anderton, BH, Breinburg, D, Downes, MJ, et al. Monoclonal anti-bodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature 1982; 298: 8486.
15.Gambetti, P, Autulio-Gambetti, L, Perry, G, et al. Antibodies to neurofibrillary tangles of Alzheimer’s disease from human and animal neurofilament fractions. Lab Invest 1983; 49: 430435.
16.Crapper, DR, Krishnan, SSDalton, AJ.Brain aluminum distribution in Alzheimer’s disease and especially neurofibrillary degeneration. Science 1973; 180: 511513.
17.Crapper, DR, Krishnan, SS, Quirrkat, S.Aluminum, neurofibrillary degeneration and Alzheimer’s disease. Brain 1976; 99: 6780.
18.Markesbury, WR, Ehmann, WD, Hossain, TIM, et al. Instrumental neutron activation analysis of brain aluminum in Alzheimer’s disease and aging. Ann Neurol 1981; 10: 511516.
19.McDermott, JR, Smith, AI, Igbal, K, et al. Brain aluminum in aging and Alzheimer disease. Neurology 1979; 29: 809814.
20.Trapp, GA, Miner, GD, Zimmerman, et al. Aluminum levels in brain in Alzheimer’s disease. Biol Psychiat 1978; 13: 709718.
21.Perl, DP.Detection of aluminum in nervous system tissues by scanning electron microscopy. In: Wills, MR, Savory, J, eds. Aluminum Analysis in Biological Materials. Charlottesville, VA: Univ. Virginia Press, 1983: 3444.
22.Perl, DP, Brody, AR.Alzheimer’s disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 1980; 208: 297299.
23.Perl, DP, Pendlebury, WW.Aluminum accumulation in neurofibril-lary tangle-bearing neurons of senile dementia, Alzheimer’s type — detection by intraneuronal X-ray spectrometry studies of unstained tissue sections. J Neuropath Exptl Neurol 1984; 43: 349.
24.Wisniewski, K, Jervis, GA, Moretz, RC, et al. Alzheimer neurofibril-lary tangles in diseases other than senile and presenile dementia. Ann Neurol 1979; 5: 288294.
25.Kurland, LT, Mulder, DW.Epidemiologic investigations of amyo-trophic lateral sclerosis. Neurology 1954; 4: 355378.
26.Hirano, A, Kurland, LT, Krooth, RS, et al. Parkinsonism-dementia complex, an endemic disease on the island of Guam. — I. Clinical features. Brain 1961; 84: 642661.
27.Hirano, A, Malamud, N, Kurland, LT.Parkinsonism-dementia comples, an endemic disease on the island of Guam. II. Pathological features. Brain 1961; 84: 662679.
28.Malamud, N, Hirano, A, Kurland, LT.Pathoanatomic changes in amyotrophic lateral sclerosis on Guam. Special reference to the occurrence of neurofibrillary changes. Arch Neurol 1961; 29: 573578.
29.Hirano, A, Arumugasamy, N, Zimmerman, HM.Amyotrophic lateral sclerosis: a comparison of Guam and classical cases. Arch Neurol 1967; 16: 357363.
30.Gajdusek, DC.Foci of motor neuron disease in high incidence in isolated populations of East Asia and the Western Pacific. In: Rowland, LP, ed. Advances in Neurology: Human Motor Neuron Diseases. New York: Raven Press, 1982; 36: 363394.
31.Perl, DP, Gajdusek, DC, Garruto, RM, et al. Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and parkinsonism dementia of Guam. Science 1982; 217: 10531054.
32.Garruto, RM, Fukatsu, R, Yangihara, R, et al. Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam. Proc Natl Acad Sci (USA) 1984; 81: 18751879.
33.Perl, DP, Munoz-Garcia, D, Good, PF, et al. Laser microprobe mass analyzer (LAMMA) — a new approach to the study of the association of aluminum and neurofibrillary tangle formation. In: Fisher, A, Hanin, I, eds. Alzheimer’s and Parkinsons’ Diseases. New York: Plenum, 1986; 241248.
34.Perl, DP, Munoz-Garcia, D, Good, PF, et al. Intracytoplasmic alumi-num accumulation in neurofibrillary tangle-bearing neurons: detection by laser microprobe mass analyzer (LAMMA). Ann Neurol 1985; 34: 264.
35.Heinen, HJ, Hillenkamp, F, Kaufmann, R, et al. LAMMA: A new laser microprobe mass analyzer for biomedicine and biological materials analysis. In: Frigerio, A, McCamish, M, eds. Recent Developments in Mass Spectometry in Biochemistry and Medicine. Amsterdam: Elsevier, 1980: 435451.
36.Perl, DP, Munoz-Garcia, D, Good, PF, et al. Calculation of intracellu-lar aluminum concentration in neurofibrillary tangle (NFT) bearing and NFT-free neurons of ALS/Parkinsonism dementia (PD) of Guam using laser microprobe mass analysis (LAMMA). J Neuropath Exptl Neurol 1986; 45: 379.
37.Underwood, EJ.Trace Elements in Human and Animal Nutrition. New York: Academic Press, 1977: p. 430.
38.Karlick, SJ, Eichhorn, GL, Lewis, PN, et al. Interaction of alumi-num species with deoxyribonucleic acid. Biochemistry 1980; 19: 59915998.
39.Lai, JCK, Blass, JP.Inhibition of brain glycolysis by aluminum. J Neurochem 1984; 42: 438446.
40.Wenk, GL, Stemmer, KL.Activity of the enzymes dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase in discrete brain regions of the copper-zinc deficient rat following aluminum ingestion. Neurotoxicology 1982; 3: 9399.
41.Marquis, JK, Lerrick, AJ.Noncompetitive inhibition by aluminum, scandium, and yttrium of acetylcholinesterase from “electro-phoruselectricus”. Biochem Pharmacology 1982; 31: 14371440.
42.Kosik, KS, Bradley, WG, Good, PF, et al. Cholinergic function in lumbar aluminum myelopathy. J Neurpath Exptl Neurol 1983; 42: 365375.
43.Yates, CM, Simpson, J, Russell, D, et al. Cholinergic enzymes in neurofibrillary degeneration produced by aluminum. Brain Res 1980; 197: 269274.
44.Siegal, N, Coughlin, R, Haug, A.A thermodynamic and electron paramagnetic resonance study of structural changes in calmodulin induced by aluminum binding. Biochem Biophys Res Comm 1983; 115: 512517.
45.Siegel, N, Suhayda, C, Haug, A.Aluminum changes the conformation of calmodulin. Physiol Chem Physics 1982; 14: 165169.
46.Heyman, A, Wilkinson, WE, Stafford, JA, et al. Alzheimer’s disease: a study of epidemiological aspects. Ann Neurol 1984; 15: 335341.
47.Yase, Y.The pathogenesis of amyotrophic lateral sclerosis. Lancet 1972; 2: 292296.
48.Reed, DM, Brody, JA.Amyotrophic lateral sclerosis and parkinson-ism-dementia on Guam, 1945–1972.1. Descriptive epidemiology. Amer J Epidemiol 1975; 101: 287301.
49.Garruto, RM, Yanagihara, R, Gajdusek, DC.Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam. Neurology 1985; 35: 193198.

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