On robust tail index estimation

Beran, Jan; Schell, Dieter

On robust tail index estimation

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Datum

2012

Publikationstyp

Zeitschriftenartikel

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Erschienen in

Computational Statistics & Data Analysis. 2012, 56(11), pp. 3430-3443. ISSN 0167-9473. Available under: doi: 10.1016/j.csda.2010.05.028

Zusammenfassung

Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer's disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid β (Aβ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased Aβ secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered Aβ release was associated with rapid upregulation of the GDNF coreceptor “rearranged during transfection” (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased Aβ, whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and Aβ increase. This suggests that RET signaling affects Aβ release from aging neurons.

Fachgebiet (DDC)

510 Mathematik

Schlagwörter

Tail index estimation, Robust estimation, Huberization, Hill estimator, Influence functional, Small sample

Zitieren

ISO 690

BERAN, Jan, Dieter SCHELL, 2012. On robust tail index estimation. In: Computational Statistics & Data Analysis. 2012, 56(11), pp. 3430-3443. ISSN 0167-9473. Available under: doi: 10.1016/j.csda.2010.05.028

BibTex

@article{Beran2012robus-23236,
  year={2012},
  doi={10.1016/j.csda.2010.05.028},
  title={On robust tail index estimation},
  number={11},
  volume={56},
  issn={0167-9473},
  journal={Computational Statistics & Data Analysis},
  pages={3430--3443},
  author={Beran, Jan and Schell, Dieter}
}

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