TY  - JOUR
A1  - Zollo, Alen
A1  - Allen, Zoe
A1  - Rasmussen, Helle F.
A1  - Iannuzzi, Filomena
A1  - Shi, Yichen
A1  - Larsen, Agnete
A1  - Maier, Thorsten Jürgen
A1  - Matrone, Carmela
T1  - Sortilin-related receptor expression in human neural stem cells derived from Alzheimer's disease patients carrying the APOE epsilon 4 allele
T2  - Neural plasticity
N2  - 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.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43730
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-437309
SN  - 1687-5443
SN  - 2090-5904
SN  - 0792-8483
N1  - 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.
VL  - [25]
IS  - Art. 1892612
SP  - 1
EP  - 10
PB  - Hindawi
CY  - New York, NY
ER  -