Sortilin-related receptor expression in human neural stem cells derived from Alzheimer's disease patients carrying the APOE epsilon 4 allele
- 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.
Author: | Alen Zollo, Zoe Allen, Helle F. Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten Jürgen MaierGND, Carmela Matrone |
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URN: | urn:nbn:de:hebis:30:3-437309 |
DOI: | https://doi.org/10.1155/2017/1892612 |
ISSN: | 1687-5443 |
ISSN: | 2090-5904 |
ISSN: | 0792-8483 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28634550 |
Parent Title (English): | Neural plasticity |
Publisher: | Hindawi |
Place of publication: | New York, NY |
Contributor(s): | Bruno Poucet |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2017/07/06 |
Date of first Publication: | 2017/05/28 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/07/06 |
Volume: | [25] |
Issue: | Art. 1892612 |
Page Number: | 11 |
First Page: | 1 |
Last Page: | 10 |
Note: | 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. |
HeBIS-PPN: | 425032124 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |