Aluminium exposure induces Alzheimer's disease-like histopathological alterations in mouse brain.
Aluminium (Al) is a neurotoxic metal and Al exposure may be a factor in the aetiology of various neurodegenerative diseases such as Alzheimer's disease (AD). The major pathohistological findings in the AD brain are the presence of neuritic plaques containing beta-amyloid (Abeta) which may interfere with neuronal communication. Moreover, it has been observed that GRP78, a stress-response protein induced by conditions that adversely affect endoplasmic reticulum (ER) function, is reduced in the brain of AD patients. In this study, we investigated the correlation between the expression of Abeta and GRP78 in the brain cortex of mice chronically treated with aluminium sulphate. Chronic exposure over 12 months to aluminium sulphate in drinking water resulted in deposition of Abeta similar to that seen in congophilic amyloid angiopathy (CAA) in humans and a reduction in neuronal expression of GRP78 similar to what has previously been observed in Alzheimer's disease. So, we hypothesise that chronic Al administration is responsible for oxidative cell damage that interferes with ER functions inducing Abeta accumulation and neurodegenerative damage.
Rodella
L F
LF
Unit of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy. rodella@med.unibs.it
Ricci
F
F
Borsani
E
E
Stacchiotti
A
A
Foglio
E
E
Favero
G
G
Rezzani
R
R
Mariani
C
C
Bianchi
R
R
D000535:Aluminum / Q000008:administration & dosage* / Q000633:toxicity; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002525:Cerebellar Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D058225:Plaque, Amyloid / Q000737:chemistry; D036401:Toxicity Tests, Chronic / Q000379:methods
D016229:Amyloid beta-Peptides; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D000535:Aluminum