Abstract

Alzheimer's disease is the most common form of age-related neurodegenerative dementia. The disease is characterised by the presence of plaques in the cerebral cortex. The major constituent of these plaques is aggregated amyloid-β peptide. This review focuses on the molecular aspects of metal complexes designed to bind to amyloid-β. The development of radioactive metal-based complexes of copper and technetium designed as diagnostic imaging agents to detect amyloid burden in the brain is discussed. Separate sections of the review discuss the use of luminescent metal complexes to act as non-conventional probes of amyloid formation and recent research into the use of metal complexes as inhibitors of amyloid formation and toxicity.

Highlights

  • Alzheimer’s disease is the most common form of age-related neurodegenerative dementia

  • This review focuses on the molecular aspects of metal complexes designed to bind to amyloid-b

  • The development of radioactive metal-based complexes of copper and technetium designed as diagnostic imaging agents to detect amyloid burden in the brain is discussed

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Summary

Brief introduction to the pathology of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative condition that results in synaptic failure and neuronal death These symptoms initially manifest as mild forgetfulness but lead to complete loss of cognition.[1] Characteristic pathological hallmarks in the brains of those suffering with the disease include the presence of extracellular senile plaques, intracellular neurofibrillary tangles and altered levels of neurotransmitters. Several elegant and sophisticated approaches that use chelating ligands designed to attenuate CuII/ZnII–Ab interactions and redistribute metal ions bound to Ab plaques that are of significant interest as potential therapeutics will not be discussed in this review but selected leading references[11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26] and reviews[27,28,29,30,31,32] are available

The amyloid-b peptide and plaques
Structural morphology of amyloid plaques
Molecules that bind to Ab fibrils and plaques
Technetium-99m radiotracers designed to bind to amyloid-b
Findings
Conclusions
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