Aluminum and Alzheimer's disease: A new look

Abstract

Despite the circumstantial and sometimes equivocal support, the hypothetic involvement of aluminum (Al) in the etiology and pathogenesis of Alzheimer's disease (AD) has subsisted in neuroscience. There are very few other examples of scientific hypotheses on the pathogenesis of a disease that have been revisited so many times, once a new method that would allow a test of Al's accumulations in the brain of AD patients or a comparison between Al-induced and AD neuropathological signs has become available. Although objects of methodological controversies for scientists and oversimplification for lay spectators, several lines of evidence have strongly supported the involvement of Al as a secondary aggravating factor or risk factor in the pathogenesis of AD. We review evidence on the similarities and dissimilarities between Al-induced neurofibrillary degeneration and paired helical filaments from AD, the accumulation of Al in neurofibrillary tangles and senile plaques from AD, the neuropathological dissociation between AD and dialysis associated encephalopathy, and the epidemiological relations between Al in drinking water and the prevalence of AD. We also critically analyze the prospects of Al-amyloid cascade studies and other evolving lines of evidence that might shed insights into the link between Al and AD. The message between the lines of the following article is that the involvement of Al in the pathogenesis of AD should not be discarded, especially in these times when the amyloid dogma of AD etiology shows its myopia.

Metal ions affect insulin-degrading enzyme activity

“…In this way, the mass spectra are simplified, while the screening of the different metal ions is faster and can be subjected to automation. We carried out enzymatic digestions of B20-30, in the presence or absence of copper(II), aluminum(III) and zinc(II), metals chosen for their important role in neurodegenerative diseases [24,26,66,67]. Moreover, since copper enters the cell as copper(I) through high-affinity plasma membrane copper transporters or low affinity permeases [68] and IDE is mainly cytosolic [1], it is interesting to analyze the effect of both oxidation states on B (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) processing.…”

Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure

“…Although the mechanisms of Al neurotoxicity are not fully understood, multiple pathways are likely to be involved in this process [9] .…”

Analyzing Nootropic Effect of <i>Phyllanthus reticulatus</i> Poir. on Cognitive Functions, Brain Antioxidant Enzymes and Acetylcholinesterase Activity against Aluminium-Induced Alzheimer’s Model in Rats: Applicable for Controlling the Risk Factors of Alzheimer’s Disease

“…Aluminium is a generally manifested neurotoxin and possesses diverse mode of action on the central nervous system (CNS) [29]. It is able to rise the permeability and crossing of the blood-brain barrier (BBB) [30] [31], which plays a significant role to increase the concentration of aluminium in the hippocampus [32], cortex, singulated bundles and corpus callosum [33].…”