Mechanisms of aluminum-induced neurodegeneration in animals: Implications for Alzheimer's disease

J Alzheimers Dis. 2006 Nov;10(2-3):135-44. doi: 10.3233/jad-2006-102-302.

Abstract

For four decades the controversial question concerning a possible role for aluminum neurotoxicity in contributing to the pathogenesis of Alzheimer's disease has been debated, and studies by different investigators have yielded contradictory results. The lack of sensitivity to aluminum neurotoxicity in transgenic mouse models of Alzheimer's disease has not allowed the system to be used to explore important aspects of this toxicity. Rabbits are particularly sensitive to aluminum neurotoxicity and they develop severe neurological changes that are dependent on dose, age and route of administration. The most prominent feature induced by aluminum in rabbit brain is a neurofibrillary degeneration that shares some similarity with the neurofibrillary tangles found in Alzheimer's disease patients. In the present review we discuss data from our laboratory and others, on the effects of aluminum on behaviour, neurologic function and morphology, using aluminum administered to rabbits via different routes. Finally, we will examine data on the possible cellular mechanisms underlying aluminum neurotoxicity, and potential neuroprotective strategies against aluminum toxicity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / drug effects
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Bcl-2-Like Protein 11
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology*
  • Disease Models, Animal*
  • Membrane Proteins / antagonists & inhibitors
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Nerve Degeneration / chemically induced*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology*
  • Neurofibrillary Tangles / drug effects
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Organometallic Compounds / toxicity*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Pyrones / toxicity*
  • Rabbits
  • bcl-2-Associated X Protein / drug effects

Substances

  • Amyloid beta-Protein Precursor
  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Membrane Proteins
  • Mitochondrial Membrane Transport Proteins
  • Organometallic Compounds
  • Proto-Oncogene Proteins
  • Pyrones
  • bcl-2-Associated X Protein
  • mitochondrial permeability transition pore
  • aluminum maltolate