Insulin growth factor binding protein 7 is a novel target to treat dementia.
Alzheimer's disease (AD) is the most common form of dementia in the elderly but effective therapeutic strategies to treat AD are not yet available. This is also due to the fact that the pathological mechanisms that drive the pathogenesis of sporadic AD are still not sufficiently understood and may differ on the individual level. Several risk factors such as altered insulin-like peptide (ILP) signaling have been linked to AD and modulating the ILP system has been discussed as a potential therapeutic avenue. Here we show that insulin-like growth factor binding protein 7 (IGFBP7), a protein that attenuates the function of ILPs, is up-regulated in the brains of AD patients and in a mouse model for AD via a process that involves altered DNA-methylation and coincides with decreased ILP signaling. Mimicking the AD-situation in wild type mice, by increasing hippocampal IGFBP7 levels leads to impaired memory consolidation. Consistently, inhibiting IGFBP7 function in mice that develop AD-like memory impairment reinstates associative learning behavior. These data suggest that IGFBP7 is a critical regulator of memory consolidation and might be used as a biomarker for AD. Targeting IGFBP7 could be a novel therapeutic avenue for the treatment of AD patients.
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany.
Hope Y
HY
Agbemenyah
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany.
Roberto C
RC
Agis-Balboa
German Center for Neurodegenerative Diseases (DZNE) Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany.
Susanne
S
Burkhardt
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
Ivana
I
Delalle
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany. Electronic address: afische2@gwdg.de.
Andre
A
Fischer
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019175:DNA Methylation; D003704:Dementia / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1
Alzheimer; Epigenetics; Insulin-like growth factor binding proteins; Learning and memory