Activity-dependent neuroprotective protein (ADNP) expression in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease

J Mol Neurosci. 2010 May;41(1):114-20. doi: 10.1007/s12031-009-9300-x. Epub 2009 Oct 21.


A major determinant in the pathogenesis of Alzheimer's disease (AD) is the deposition of beta-amyloid (Abeta) peptides in specific areas of the central nervous system. Therefore, animal models of Alzheimer amyloidosis are excellent tools to identify candidates to facilitate drug screening and to understand the molecular pathology of AD. Activity-dependent neuroprotective protein (ADNP) plays an essential role in brain development, and NAP (NAPVSIPQ, generic name: davunetide)--a peptide derived from ADNP--is currently in clinical development for the treatment of neurodegenerative disorders. However, the link between ADNP expression and AD remains unexplored. To test whether ADNP is affected by the onset of AD and progression, we employed the PS1xAPP mouse model (PS1(M146L) x APP(751SL) transgenic mice) to analyze the mRNA expression of ADNP in the hippocampus and cerebellum in early and advanced stages of disease. Results showed that ADNP expression in 6-month-old PS1xAPP mice hippocampus was higher than in wild-type (WT) mice. ADNP was originally identified as a vasoactive intestinal peptide (VIP)-responsive gene taking part in the VIP-mediated neurotrophic pathway. Interestingly, the expression of VIP was not affected in the same experimental setting, suggesting that ADNP expression is a VIP-independent marker associated with AD. Moreover, in the cerebellum, a brain area not affected by Abeta deposition, ADNP mRNA expression in 6-month-old PS1xAPP and WT were not different. A similar extent of hippocampal ADNP expression was observed in 18-month-old WT and PS1xAPP mice, in contrast to the differential expression level at 6 months of age. However, hippocampal ADNP expression in both WT and PS1xAPP was increased with aging similar to VIP mRNA expression. Our findings support the hypothesis that ADNP expression is related to early or mild AD progression by a VIP-independent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Disease Models, Animal
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism*
  • Presenilin-1 / metabolism*
  • Vasoactive Intestinal Peptide / metabolism


  • Adnp protein, mouse
  • Amyloid beta-Protein Precursor
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Presenilin-1
  • Vasoactive Intestinal Peptide