Analysis of peripheral amyloid precursor protein in Angelman Syndrome

Craig A. Erickson, Logan K. Wink, Bayon Baindu, Balmiki Ray, Tori L. Schaefer, Ernest V. Pedapati, Debomoy Lahiri

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Angelman Syndrome is a rare neurodevelopmental disorder associated with significant developmental and communication delays, high risk for epilepsy, motor dysfunction, and a characteristic behavioral profile. While Angelman Syndrome is known to be associated with the loss of maternal expression of the ubiquitin-protein ligase E3A gene, the molecular sequelae of this loss remain to be fully understood. Amyloid precursor protein (APP) is involved in neuronal development and APP dysregulation has been implicated in the pathophysiology of other developmental disorders including fragile X syndrome and idiopathic autism. APP dysregulation has been noted in preclinical model of chromosome 15q13 duplication, a disorder whose genetic abnormality results in duplication of the region that is epigenetically silenced in Angelman Syndrome. In this duplication model, APP levels have been shown to be significantly reduced leading to the hypothesis that enhanced ubiquitin-protein ligase E3A expression may be associated with this phenomena. We tested the hypothesis that ubiquitin-protein ligase E3A regulates APP protein levels by comparing peripheral APP and APP derivative levels in humans with Angelman Syndrome to those with neurotypical development. We report that APP total, APP alpha (sAPPα) and A Beta 40 and 42 are elevated in the plasma of humans with Angelman Syndrome compared to neurotypical matched human samples. Additionally, we found that elevations in APP total and sAPPα correlated positively with peripheral brain derived neurotrophic factor levels previously reported in this same patient cohort. Our pilot report on APP protein levels in Angelman Syndrome warrants additional exploration and may provide a molecular target of treatment for the disorder.

Original languageEnglish (US)
Pages (from-to)2334-2337
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume170
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Angelman Syndrome
Amyloid beta-Protein Precursor
Ubiquitin-Protein Ligases
Chromosome Duplication
Fragile X Syndrome
Inborn Genetic Diseases
Brain-Derived Neurotrophic Factor
Autistic Disorder

Keywords

  • amyloid precursor protein
  • Angelman Syndrome
  • brain derived neurotrophic factor
  • UBE3A

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Erickson, C. A., Wink, L. K., Baindu, B., Ray, B., Schaefer, T. L., Pedapati, E. V., & Lahiri, D. (2016). Analysis of peripheral amyloid precursor protein in Angelman Syndrome. American Journal of Medical Genetics, Part A, 170(9), 2334-2337. https://doi.org/10.1002/ajmg.a.37811

Analysis of peripheral amyloid precursor protein in Angelman Syndrome. / Erickson, Craig A.; Wink, Logan K.; Baindu, Bayon; Ray, Balmiki; Schaefer, Tori L.; Pedapati, Ernest V.; Lahiri, Debomoy.

In: American Journal of Medical Genetics, Part A, Vol. 170, No. 9, 01.09.2016, p. 2334-2337.

Research output: Contribution to journalArticle

Erickson, CA, Wink, LK, Baindu, B, Ray, B, Schaefer, TL, Pedapati, EV & Lahiri, D 2016, 'Analysis of peripheral amyloid precursor protein in Angelman Syndrome', American Journal of Medical Genetics, Part A, vol. 170, no. 9, pp. 2334-2337. https://doi.org/10.1002/ajmg.a.37811
Erickson CA, Wink LK, Baindu B, Ray B, Schaefer TL, Pedapati EV et al. Analysis of peripheral amyloid precursor protein in Angelman Syndrome. American Journal of Medical Genetics, Part A. 2016 Sep 1;170(9):2334-2337. https://doi.org/10.1002/ajmg.a.37811
Erickson, Craig A. ; Wink, Logan K. ; Baindu, Bayon ; Ray, Balmiki ; Schaefer, Tori L. ; Pedapati, Ernest V. ; Lahiri, Debomoy. / Analysis of peripheral amyloid precursor protein in Angelman Syndrome. In: American Journal of Medical Genetics, Part A. 2016 ; Vol. 170, No. 9. pp. 2334-2337.
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