RT journal article
T1 Activity-dependent neuroprotective protein (ADNP) expression in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease.
A1 Fernández-Montesinos, Rafael
A1 Torres, Manuel
A1 Baglietto-Vargas, David
A1 Gutierrez, Antonia
A1 Gozes, Illana
A1 Vitorica, Javier
A1 Pozo, David
A2 Anatomía y Embriología Humana
K1 Alzheimer’s disease
K1 Neuropeptides
K1 VIP
K1 ADNP
K1 Presenilins
K1 neurodegeneration
K1 biomarkers
AB 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.
PB John Wiley and Sons
SN 1582-1838
YR 2009
FD 2009-10-21
LK http://hdl.handle.net/10498/38831
UL http://hdl.handle.net/10498/38831
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026