A novel functional low-density lipoprotein receptor-related protein 6 gene alternative splice variant is associated with Alzheimer's disease

Marcelo A. Alarcón, Matías A. Medina, Qubai Hu, Miguel E. Avila, Bernabé I. Bustos, Eduardo Pérez-Palma, Alexis Peralta, Paulina Salazar, Giorgia D. Ugarte, Ariel E. Reyes, George M. Martin, Carlos Opazo, Randall T. Moon, Giancarlo V. De Ferrari

Resultado de la investigación: Contribución a una revistaArtículo

19 Citas (Scopus)

Resumen

We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6Δ3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6Δ3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/β-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6Δ3 isoform is a novel splice variant, which shows diminished Wnt/β-catenin signaling activity and might have a functional role in individuals with AD.

Idioma originalInglés
PublicaciónNeurobiology of Aging
Volumen34
N.º6
DOI
EstadoPublicada - 1 jun 2013

Áreas temáticas de ASJC Scopus

  • Neurociencia (todo)
  • Estudio del envejecimiento
  • Neurología clínica
  • Biología del desarrollo
  • Geriatría y gerontología

Huella Profundice en los temas de investigación de 'A novel functional low-density lipoprotein receptor-related protein 6 gene alternative splice variant is associated with Alzheimer's disease'. En conjunto forman una huella única.

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    Alarcón, M. A., Medina, M. A., Hu, Q., Avila, M. E., Bustos, B. I., Pérez-Palma, E., Peralta, A., Salazar, P., Ugarte, G. D., Reyes, A. E., Martin, G. M., Opazo, C., Moon, R. T., & De Ferrari, G. V. (2013). A novel functional low-density lipoprotein receptor-related protein 6 gene alternative splice variant is associated with Alzheimer's disease. Neurobiology of Aging, 34(6). https://doi.org/10.1016/j.neurobiolaging.2012.11.004