Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-05-31T04:12:15.961Z Has data issue: false hasContentIssue false
  • English
  • Français

A Reexamination of Aluminum in Alzheimer's Disease: Analysis by Energy Dispersive X-ray Microprobe and Flameless Atomic Absorption Spectrophotometry

Published online by Cambridge University Press:  18 September 2015

Roland W. Jacobs ,
Taihung Duong ,
Robert E. Jones ,
George A. Trapp  and
Arnold B. Scheibel
Roland W. Jacobs*
Affiliation:
Departments of Psychiatry, UCLA Brain Research Institute, UCLA Valley Hospital Medical Center, Van Nuys, CA
Taihung Duong
Affiliation:
Departments of Anatomy, UCLA
Robert E. Jones
Affiliation:
Departments of Earth and Space Sciences, UCLA
George A. Trapp
Affiliation:
VA Medical Center and Dept. of Psychiatry, Univ. of Texas Southwestern Med. School, Dallas
Arnold B. Scheibel
Affiliation:
Departments of Psychiatry, UCLA Departments of Anatomy, UCLA Brain Research Institute, UCLA
*
c/o Arnold B. Scheibel, M.D., Department of Anatomy, UCLA Center for Health Sciences, Los Angeles, CA, U.S.A. 90024
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We have attempted to verify the presence of increased aluminum (Al) levels in Alzheimer's disease (AD) brains by energy dispersive X-ray microanalysis (EDX) and flameless atomic absorption spectrophotometry (AAS). Tissue from seven AD brains, mounted on carbon polymerized coverslips, were stained with Congored or treated immunohistochemically to allow optical localization of AD-associated lesions during EDX. Despite a demonstrated sensitivity of 20-25 ppm, we were unable to detect Al in either plaque cores or neurons containing neurofibrillary tangles. For AAS, wet weight samples (ranging from 48-144 mg) from six of the seven AD brains and four controls were selected from regions similar to those studied under EDX, i.e., Brodmann areas 9, 11, 28, 46, 47, and the hippocampus. The tissue surrounding each sample site was sectioned and stained for thioflavin S. Both controls and AD samples revealed similar levels of Al ranging from undetectable to 1.80 ng/mg wet wt. (mean AD: 0.28 ± 0.39 (SD), control: 0.54 ± 0.58 (SD)), independent of degree of histopathology or age of the case. We conclude that the combined strengths of these two techniques on similar tissue specimens demonstrate that abnormal Al levels are not required to produce the histologic findings of AD and that this element may not accumulate in the aging brain. It is unlikely, therefore, that Al is essential in the etiology of pathogenesis of plaques and tangles in AD. Al's role as a primary or secondarily associated event, when present, needs further delineation.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 16 , Issue S4 , November 1989 , pp. 498 - 503
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

References

REFERENCES

1.Candy, JM, Edwardson, JA, Klinowski, J, et al. Co-localization 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. Berlin: Springer-Verlag, 1985: 183–197.CrossRefGoogle Scholar
2.Candy, JM, Klinowski, J, Perry, RH, et al. Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1986; 1: 354–356.CrossRefGoogle ScholarPubMed
3.Crapper, DR, Krishnan, SS, Dalton, AJ. Brain aluminum distribution in Alzheimer’s disease and experimental neurofibrillary degeneration. Science 1973; 180: 511–513.CrossRefGoogle ScholarPubMed
4.Crapper, DR, Krishnan, SS, Quittkat, S. Aluminum, neurofibrillary degeneration and Alzheimer’s disease. Brain 1976; 99: 67–80.CrossRefGoogle ScholarPubMed
5.Duckett, S, Galle, P. Mise en évidence de l’aluminum dans les plaqus de la maladie d’Alzheimer: Etudie a la microsonde de Castaing. C R Seances Acad Sci [D] 1976; 282: 393–395.Google Scholar
6.Markesbery, WR, Ehmann, WD, Hossain, TIM, et al. Instrumental neutron activation analysis of brain aluminum in Alzheimer disease and aging. Ann Neurol 1981; 10: 511–516.CrossRefGoogle ScholarPubMed
7.Masters, CL, Multhaup, G, Simms, G, et al. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessel. EMBO J 1985; 4: 2757–2763.CrossRefGoogle Scholar
8.Mcdermott, JR, Smith, AI, Iqbal, K, et al. Aluminum and Alzheimer’s disease. Lancet 1977; 2: 710–711.CrossRefGoogle ScholarPubMed
9.Mcdermott, JR, Smith, AI, Iqbal, K, et al. Brain aluminum in aging and Alzheimer disease. Neurology 1979; 29: 809–814.CrossRefGoogle ScholarPubMed
10.Moretz, RC, Iqbal, K, Wisniewski, HM. Microanalysis of Alzheimer disease NFT and plaques. Envir Geochem Health (in press).Google Scholar
11.Perl, DP, Brody, A. Alzheimer’s disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 1980; 208: 297–299.CrossRefGoogle ScholarPubMed
12.Perl, DP, Pendlebury, WW. Aluminum accumulation in neurofibrillary tangle-bearing neurons of senile dementia, Alzheimer’s type (SDAT)-detection by intraneuronal X-ray spectrometry studies of unstained tissue sections. J Neuropath Exp Neurol 1984; 43: 349.CrossRefGoogle Scholar
13.Perl, DP, Good, PF. Laser Microprobe Mass (LAMMA) Analysis evidence that aluminum (Al) selectively accumulates in the neurofibrillary tangle (NFT). J Neuropath Exp Neurol 1988; 47: 318.Google Scholar
14.Iqbal, K, Alauddin, M. Trace metal analysis of plaques and tangles in Alzheimer’s disease. Alzheimer Dis Assoc Disord 1988; 2: 316.Google Scholar
15.Stern, AJ, Perl, DP, Munoz-Garcia, D, et al. Investigation of silicon and aluminum content in isolated senile plaque cores by laser microprobe mass analysis (LAMMA). J Neuropath Exp Neurol 1987; 45: 361.CrossRefGoogle Scholar
16.Trapp, GA, Miner, GD, Zimmerman, RL. Aluminum levels in brain in Alzheimer’s disease. Biol Psychiatry 1978; 13: 709–718.Google ScholarPubMed
17.Klatzo, I, Wisniewski, H, Streicher, E. Experimental production of neurofibrillary degeneration: 1. Light microscopic observation. J Neuropathol Exp Neurol 1965; 24: 187–199.CrossRefGoogle Scholar
18.Terry, RD, Pena, C. Experimental production of neurofibrillary degeneration: 2. Electron microscopy, phosphatase histochemistry and electron probe analysis. J Neuropathol Exp Neurol 1965; 24: 200–210.CrossRefGoogle ScholarPubMed
19.Terry, RD. The fine structure of neurofibrillary tangles in Alzheimer’s disease. J Neuropathol Exp Neurol 1963; 22: 629–642.CrossRefGoogle ScholarPubMed
20.Ihara, Y, Abraham, C, Selkoe, DJ. Antibodies to paired helical filaments in Alzheimer’s disease do not recognize normal brain proteins. Nature 1983; 304: 727–730.CrossRefGoogle Scholar
21.Alfrey, AC, Legendre, G, Kaehny, WD. The dialysis encephalopathy syndrome. N Engl J Med 1976; 294: 184–188.CrossRefGoogle Scholar
22.Arieff, AI, Cooper, JD, Armstrong, D, et al. Dementia, renal failure, and brain aluminum. Ann Intern Med 1979; 90: 741–747.CrossRefGoogle ScholarPubMed
23.Perl, DP, Gajdusek, DC, Garruto, RM, et al. Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism dementia of Guam. Science 1982; 217: 1053.CrossRefGoogle ScholarPubMed
24.Perl, DP, Munoz-Garcia, D, Good, P, et al. Laser Microprobe Mass Analyzer (LAMMA) - A new approach to the study of the association of aluminum and neurofibrillary tangle formation. In: Fisher, F, Hanin, I, Lachman, C, eds. Alzheimer’s and Parkinson’s Diseases: Strategies for Research and Development. New York: Plenum Press, 1986: 241–248.CrossRefGoogle Scholar
25.Garruto, RM, Fukatsu, R, Yanagihara, R, et al. Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam. Proc Natl Acad Sci 1984; 81: 1875–1879.CrossRefGoogle ScholarPubMed
26.Garruto, RM, Yase, Y. Neurodegenerative disorders of the western Pacific: The search for mechanisms of pathogenesis. TINS 1986; 9: 368–374.Google Scholar
27.Cummings, JL, Benson, DF. Cortical dementias: Alzheimer and Pick diseases. In: Dementia: A Clinical Approach. Boston: Butterworths, 1983: 35–72.Google Scholar
28.Katzman, R. Alzheimer’s disease. N Engl J Med 1986; 314: 964–973.Google Scholar
29.Crapper, DR, Quittkat, S, Krishnan, SS, et al. Intranuclear aluminum content in Alzheimer’s disease, dialysis encephalopathy and experimental aluminum encephalopathy. Acta Neuropathol (Beri) 1980; 50: 19–24.CrossRefGoogle ScholarPubMed
30.Krishnan, SS, Harrison, JE, Crapper Mclachlan, DR. Origin and resolution of the aluminum controversy concerning Alzheimer’s neurofibrillary degeneration. Bio Trace Elem Res 1987; 13: 35–42.CrossRefGoogle ScholarPubMed
31.Trapp, GA. Elimination of chloride interference in electrothermal atomic absorption analysis of serum aluminum. Anal Biochem (in press).Google Scholar
32.Jacobs, RW, Duong, T, Scheibel, AB. A reexamination of aluminum in Alzheimer’s disease. Soc Neurosci Abstr 1988; 14: 1083.Google Scholar
33.Scheibel, AB, Pommier, E, Duong, T. Immunodetection of human serum amyloid P-component in Alzheimer’s disease. Soc Neurosci Abstr 1987; 13: 1152.Google Scholar