Targeting Metal Homeostasis as a Therapeutic Strategy for Alzheimer’s Disease

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Antonietta Vilella
Eleonora Daini
Chiara De Benedictis
Andreas Grabrucker


Trace metals play an important role in the pathophysiology of amyloid precursor protein, amyloid beta, and tau, the key molecules involved in Alzheimer’s disease. Altering trace metal concentrations in the brain has been explored as a therapeutic strategy for Alzheimer’s disease. It is not only the accumulation of metals that drives amyloid beta aggregation, but also the lack of sufficient trace metals for other biological processes created through sequestration by amyloid beta that affects brain health and function. Thus, balancing metal levels to achieve therapeutic effects is an intricate process. This chapter summarizes the role of trace metals in Alzheimer’s disease and highlights the preclinical and clinical studies targeting metal homeostasis in animal models and humans. It further discusses recent developments in pharmacological approaches targeting metals in Alzheimer’s disease and provides an outlook on possible future treatments based on current translational research, for example, nanomedicine.


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Chapter 5