Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders

Curr Alzheimer Res. 2012 Jan;9(1):5-17. doi: 10.2174/156720512799015064.


Alzheimer's disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer's disease, Huntington's disease, and Parkinson's disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and 'eumetabolic' activities may possess superior efficacies compared to less pluripotent remedies.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adiponectin / metabolism
  • Alzheimer Disease / complications*
  • Alzheimer Disease / metabolism*
  • Body Weight
  • Brain-Derived Neurotrophic Factor / metabolism
  • Ghrelin / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose / metabolism
  • Humans
  • Leptin / metabolism
  • Metabolic Diseases / etiology*
  • Neurodegenerative Diseases / complications*
  • Neurodegenerative Diseases / metabolism*


  • Adiponectin
  • Brain-Derived Neurotrophic Factor
  • Ghrelin
  • Leptin
  • Glucagon-Like Peptide 1
  • Glucose