Aβ and human amylin share a common toxicity pathway via mitochondrial dysfunction

Yun An Lim, Virginie Rhein, Ginette Baysang, Fides Meier, Anne Poljak, Mark J. Raftery, Michael Guilhaus, Lars M. Ittner, Anne Eckert, Jürgen Götz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)


Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are leading causes of morbidity and mortality in the elderly. Both diseases are characterized by amyloid deposition in target tissues: aggregation of amylin in T2DM is associated with loss of insulin-secreting β-cells, while amyloid β (Aβ) aggregation in AD brain is associated with neuronal loss. Here, we used quantitative iTRAQ proteomics as a discovery tool to show that both Aβ and human amylin (HA) deregulate identical proteins, a quarter of which are mitochondrial, supporting the notion that mitochondrial dysfunction is a common target in these two amyloidoses. A functional validation revealed that mitochondrial complex IV activity was significantly reduced after treatment with either HA or Aβ, as was mitochondrial respiration. In comparison, complex I activity was reduced only after treatment with HA. Aβ and HA, but not the non-amyloidogenic rat amylin, induced significant increases in the generation of ROS. Co-incubation of HA and Aβ did not produce an augmented effect in ROS production, again suggesting common toxicity mechanisms. In conclusion, our data suggest that Aβ and HA both exert toxicity, at least in part, via mitochondrial dysfunction, thus restoring their function may be beneficial for both AD and T2DM.

Original languageEnglish
Pages (from-to)1621-1633
Number of pages13
Issue number8
Publication statusPublished - 1 Apr 2010
Externally publishedYes


  • Alzheimer's disease
  • Amyloidosis
  • Mitochondrial complex proteins
  • Respiration
  • Type 2 diabetes mellitus


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