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-...

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Veröffentlicht in:Neural plasticity. - 1998. - 2017(2017) vom: 28., Seite 1892612
1. Verfasser: Zollo, Alen (VerfasserIn)
Weitere Verfasser: Allen, Zoe, Rasmussen, Helle F, Iannuzzi, Filomena, Shi, Yichen, Larsen, Agnete, Maier, Thorsten J, Matrone, Carmela
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Neural plasticity
Schlagworte:Journal Article Amyloid beta-Peptides Apolipoprotein E4 LDL-Receptor Related Proteins Membrane Transport Proteins SORL1 protein, human
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520 |a 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 
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650 7 |a Amyloid beta-Peptides  |2 NLM 
650 7 |a Apolipoprotein E4  |2 NLM 
650 7 |a LDL-Receptor Related Proteins  |2 NLM 
650 7 |a Membrane Transport Proteins  |2 NLM 
650 7 |a SORL1 protein, human  |2 NLM 
700 1 |a Allen, Zoe  |e verfasserin  |4 aut 
700 1 |a Rasmussen, Helle F  |e verfasserin  |4 aut 
700 1 |a Iannuzzi, Filomena  |e verfasserin  |4 aut 
700 1 |a Shi, Yichen  |e verfasserin  |4 aut 
700 1 |a Larsen, Agnete  |e verfasserin  |4 aut 
700 1 |a Maier, Thorsten J  |e verfasserin  |4 aut 
700 1 |a Matrone, Carmela  |e verfasserin  |4 aut 
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773 1 8 |g volume:2017  |g year:2017  |g day:28  |g pages:1892612 
856 4 0 |u http://dx.doi.org/10.1155/2017/1892612  |3 Volltext 
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