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Insulin growth factor binding protein 7 is a novel target to treat dementia

Hope Y Agbemenyah1, Roberto C Agis-Balboa1, Susanne Burkhardt2

  • 1Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany.

Neurobiology of Disease
|October 1, 2013
PubMed

Insights

Alzheimer's disease (AD) involves altered insulin-like peptide (ILP) signaling. Researchers found increased insulin-like growth factor binding protein 7 (IGFBP7) in AD brains, impairing memory and suggesting IGFBP7 as a therapeutic target.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is a leading cause of dementia with limited effective treatments.
  • Pathogenesis of sporadic AD is complex and not fully understood, with altered insulin-like peptide (ILP) signaling identified as a risk factor.
  • Modulating ILP system activity is a potential therapeutic strategy for AD.

Purpose of the Study:

  • To investigate the role of insulin-like growth factor binding protein 7 (IGFBP7) in Alzheimer's disease pathogenesis.
  • To determine if IGFBP7 levels correlate with AD progression and cognitive decline.
  • To explore IGFBP7 as a potential biomarker and therapeutic target for AD.

Main Methods:

  • Quantification of IGFBP7 expression in post-mortem human AD brains and an AD mouse model.
  • Analysis of DNA methylation patterns associated with IGFBP7 up-regulation.
  • Experimental manipulation of hippocampal IGFBP7 levels in wild-type and AD model mice to assess memory function.

Main Results:

  • IGFBP7 is significantly up-regulated in the brains of AD patients and in an AD mouse model.
  • Increased IGFBP7 levels correlate with decreased ILP signaling and are linked to altered DNA methylation.
  • Elevated hippocampal IGFBP7 in mice impairs memory consolidation, while inhibiting IGFBP7 function restores memory in AD models.

Conclusions:

  • IGFBP7 is a key regulator of memory consolidation and its up-regulation is implicated in AD.
  • IGFBP7 may serve as a valuable biomarker for AD diagnosis and progression.
  • Targeting IGFBP7 presents a novel therapeutic strategy for treating Alzheimer's disease.
Keywords:
AlzheimerEpigeneticsInsulin-like growth factor binding proteinsLearning and memory

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