Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Publication, non-guideline, non-GLP study.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
New evidence for an active role of aluminum in Alzheimer's disease
Author:
Crapper McLachlan DR et al.
Year:
1989
Bibliographic source:
Can. J. Neurol. Sci. 16; 490-497

Materials and methods

Results and discussion

Applicant's summary and conclusion

Conclusions:
Application of molecular biological techniques and sensitive elemental analysis have produced new evidence implicating aluminium as an important factor in down regulation of neuronal protein metabolism. Aluminium in Alzheimer's disease may act by electrostatically crosslinking proteins, particularly the methionine containing histone H 1 °, and DNA.
Executive summary:

Application of molecular biological techniques and sensitive elemental analysis have produced new evidence implicating aluminium as an important factor in down regulation of neuronal protein metabolism. Aluminium Alzheimer's disease may act by electrostatically crosslinking proteins, particularly the methionine containing histone H 1 °, and DNA. The consequence of such crosslinking is reduced transcription of at least one neuron specificgene, the low molecular weight component of neurofilaments. In the superior temporal gynis in Alzheimer's disease,down regulation of this gene occurs in approximately 86% of surviving neurons and, therefore, aluminium must be considered as having an active role in the pathogenesis. Epidemiological studies are reviewed that independently support the hypothesis that environmental aluminium is a significant risk factor. Preliminary evidence also suggests that a disorder in phosphorylation may be an important initiating factor.