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Neural Plasticity
Volume 2017, Article ID 1892612, 10 pages
Research Article

Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer’s Disease Patients Carrying the APOE Epsilon 4 Allele

1Department of Biomedicine, University of Aarhus, 6 Bartholins Allé, 8000 Aarhus, Denmark
2Department of Science and Technology, University of Sannio, 82100 Benevento, Italy
3Axol Bioscience, Chesterford Research Park, Little Chesterford Cambridgeshire, Cambridge CB10 1XL, UK
4Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany

Correspondence should be addressed to Carmela Matrone;

Received 2 November 2016; Revised 31 January 2017; Accepted 22 March 2017; Published 28 May 2017

Academic Editor: Bruno Poucet

Copyright © 2017 Alen Zollo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer’s disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing. Recent in vitro evidence has associated the APOE4 allele and alterations in the SORL1 pathway with AD development and progression. Here, we analyzed SORL1 expression in neural stem cells (NSCs) from AD patients carrying null, one, or two copies of the APOE4 allele. We show reduced SORL1 expression only in NSCs of a patient carrying two copies of APOE4 allele with increased Aβ/SORL1 localization along the degenerated neurites. Interestingly, SORL1 binding to APP was largely compromised; this could be almost completely reversed by γ-secretase (but not β-secretase) inhibitor treatment. These findings may yield new insights into the complex interplay of SORL1 and AD pathology and point to NSCs as a valuable tool to address unsolved AD-related questions in vitro.