Alzheimer’s Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies

Jonathan Chang Cheng Shieh, Pai Tsang Huang, Yung Feng Lin

Research output: Contribution to journalReview articlepeer-review

66 Citations (Scopus)


Alzheimer’s (or Alzheimer) disease (AD) is the most prevalent subset of dementia, affecting elderly populations worldwide. The cumulative costs of the AD care are rapidly accelerating as the average lifespan increases. Onset and risk factors for AD and AD-like dementias have been largely unknown until recently. Studies show that chronic type II diabetes mellitus (DM) is closely associated with neurodegeneration, especially AD. Type II DM is characterized by the cells’ inability to take up insulin, as well as chronic hyperglycemia. In the central nervous system, insulin has crucial regulatory roles, while chronic hyperglycemia leads to formation and accumulation of advanced glycation end products (AGEs). AGEs are the major contributor to insulin resistance in diabetic cells, due to their regulatory role on sirtuin expression. Insulin activity in the central nervous system is known to interact with key proteins affected in neurodegenerative conditions, such as amyloid-β precursor protein (AβPP or APP), huntingtin-associated protein-1 (HAP1), Abelson helper integration site-1 (AHI1 or Jouberin), kinesin, and tau. Sirtuins have been theorized to be the mechanism for insulin resistance, and have been found to be affected in neurodegenerative conditions as well. There are hints that all these neuronal proteins may be closely related, although the mechanisms remain unclear. This review will gather existing research on these proteins and highlight the link between neurodegenerative conditions and diabetes mellitus.

Original languageEnglish
Pages (from-to)1966-1977
Number of pages12
JournalMolecular Neurobiology
Issue number4
Publication statusPublished - Apr 1 2020


  • Abelson helper integration site-1 (AHI1 or Jouberin)
  • Advanced glycation end products (AGEs)
  • Alzheimer’s (Alzheimer) disease (AD)
  • Amyloid-β precursor protein (AβPP or APP)
  • Diabetes mellitus (DM)
  • Huntingtin-associated protein-1 (HAP1)
  • Insulin resistance
  • Kinesin
  • Signal Transduction
  • Humans
  • Insulin Resistance
  • Animals
  • Insulin/metabolism
  • Nerve Degeneration/pathology
  • Alzheimer Disease/metabolism
  • Diabetes Mellitus/metabolism

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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