Amyloid-beta alters trafficking of internalized acetylcholinesterase and dextran

William Hu, Noah W. Gray, Stephen Brimijoin

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Amyloid-beta (Aβ), the main peptide constituent of senile plaques, is a suspected pathogenic mediator in Alzheimer's Disease (AD). Plaques also contain acetylcholinesterase (AChE), which may promote A. toxicity. We previously found that Aβ increased AChE levels in neuron-like N1E.115 neuroblastoma cells by reducing AChE degradation and surface shedding. Here we show that Aβ also alters the intracellular fate of surface AChE. When surface AChE was tagged with FITC-conjugated Fasciculin II (FasII), fluorescence gradually accumulated in intracellular particles. In the presence of extracellular Aβ this accumulation increased and shifted from the juxtanuclear zone to more peripheral cytoplasm. The cytoplasmic FasII-positive structures were positive for Lysosomal-Associated Membrane Protein 1, identifying them as late endosomes and early lysosomes. Thus, surface AChE trafficked into the lysosomal compartment, but further transport was impaired. Aβ also affected the transport or disposition of fluorescent dextran, an index of pinocytosis, and caused a 60% increase in intracellular accumulation similar to the lysosomotropic effects of chloroquine. On the other hand, Aβ caused no apparent changes in clathrin- and caveolaemediated endocytosis. Overall it appears that selective alteration of endocytic mechanisms and an accumulation of organelles containing improperly processed substrates might contribute to the neuronal damage associated with age and disease-related accumulation of neurotoxic Aβ in the human brain.

Original languageEnglish (US)
Pages (from-to)15-24
Number of pages10
JournalInternational Journal of Physiology, Pathophysiology and Pharmacology
Volume1
Issue number1
StatePublished - Dec 1 2009

Keywords

  • Alzheimer's disease
  • Endocytosis
  • Lysosome
  • Pinocytosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Physiology
  • Physiology (medical)

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