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

Abstract

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.

Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration

“…To eliminate the likelihood that the same cell would be counted twice, slices for each histological experiment were drawn from only one well of the collection dish to ensure that sections were at least 250 μm apart. Regions of interest for cell counts were defined using landmarks and reference points from mouse spinal cord and brain stereotaxic atlases [39,40]. In the spinal cord, only cells which were anterior to the central canal and deep apex where the grey and white matters meet were considered as part of the ventral horns; conversely, only cells which were posterior to the central canal and the posterior deep apex were considered as part of the dorsal horns.…”

Aluminum Maltolate-Induced Toxicity in NT2 Cells Occurs Through Apoptosis and Includes Cytochrome c Release

“…This Al overload resulted in a fatal neurological syndrome (dialysis dementia) and a devastating metabolic bone disease known as dialysis osteodystrophy (reviewed by Mach et al, 1988). Al has been linked to neurotoxicity (Levesque et al, 2000;Perl and Pendlebury, 1986;Roll et al, 1989;SuarezFernandez et al, 1999;Troncoso et al, 1985;Tsubouchi et al, 2001) and implicated as a possible causative or contributing factor in neurodegenerative disorders particularly Alzheimer's disease (AD), although the exact mechanism by which it acts is far from clear (Crapper McLachlan, 1986;Shin et al, 1995;Strong, 2001).…”

Review article What causes alzheimer’s disease?

“…Studies have either reported [61], or not reported [109], Al in association with the cores of classic Ab deposits, but it is not clear whether this type of SP is especially frequent in AD [18]. Al has also been detected in pyramidal neurons containing NFT [142,143]. It has been suggested that Al can bind to DNA and affect processing of cytoskeletal proteins resulting in the formation of NFT.…”