PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model

Next-generation sequencing studies have reported that rare variants in PLD3 were associated with increased risk of late-onset Alzheimer’s disease (LOAD) in European cohorts. The association has been replicated in a Han Chinese cohort, two rare variants p.I163M in exon7 and p.R356H in exon11 of PLD3...

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Autores principales: Tan, Mengshan, Li, Jieqiong, Ma, Fangchen, Zhang, Xing, Zhao, Qingfei, Cao, Xipeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382672/
https://www.ncbi.nlm.nih.gov/pubmed/30837833
http://dx.doi.org/10.3389/fnins.2019.00116
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author Tan, Mengshan
Li, Jieqiong
Ma, Fangchen
Zhang, Xing
Zhao, Qingfei
Cao, Xipeng
author_facet Tan, Mengshan
Li, Jieqiong
Ma, Fangchen
Zhang, Xing
Zhao, Qingfei
Cao, Xipeng
author_sort Tan, Mengshan
collection PubMed
description Next-generation sequencing studies have reported that rare variants in PLD3 were associated with increased risk of late-onset Alzheimer’s disease (LOAD) in European cohorts. The association has been replicated in a Han Chinese cohort, two rare variants p.I163M in exon7 and p.R356H in exon11 of PLD3 were found to be associated with LOAD risk. Whether these variants have deleterious effects on protein function, and the underlying mechanisms by which they influence LOAD pathogenesis are unknown. Our results are the first to validate the hypothesis that these variants could lead to reduced PLD3 activity and affect amyloid-β levels in cellular model of AD, possibly via autophagy-dependent mTOR signaling pathway, indicating that PLD3 may represent a new therapeutic target for AD.
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spelling pubmed-63826722019-03-05 PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model Tan, Mengshan Li, Jieqiong Ma, Fangchen Zhang, Xing Zhao, Qingfei Cao, Xipeng Front Neurosci Neuroscience Next-generation sequencing studies have reported that rare variants in PLD3 were associated with increased risk of late-onset Alzheimer’s disease (LOAD) in European cohorts. The association has been replicated in a Han Chinese cohort, two rare variants p.I163M in exon7 and p.R356H in exon11 of PLD3 were found to be associated with LOAD risk. Whether these variants have deleterious effects on protein function, and the underlying mechanisms by which they influence LOAD pathogenesis are unknown. Our results are the first to validate the hypothesis that these variants could lead to reduced PLD3 activity and affect amyloid-β levels in cellular model of AD, possibly via autophagy-dependent mTOR signaling pathway, indicating that PLD3 may represent a new therapeutic target for AD. Frontiers Media S.A. 2019-02-14 /pmc/articles/PMC6382672/ /pubmed/30837833 http://dx.doi.org/10.3389/fnins.2019.00116 Text en Copyright © 2019 Tan, Li, Ma, Zhang, Zhao and Cao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Tan, Mengshan
Li, Jieqiong
Ma, Fangchen
Zhang, Xing
Zhao, Qingfei
Cao, Xipeng
PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
title PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
title_full PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
title_fullStr PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
title_full_unstemmed PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
title_short PLD3 Rare Variants Identified in Late-Onset Alzheimer’s Disease Affect Amyloid-β Levels in Cellular Model
title_sort pld3 rare variants identified in late-onset alzheimer’s disease affect amyloid-β levels in cellular model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382672/
https://www.ncbi.nlm.nih.gov/pubmed/30837833
http://dx.doi.org/10.3389/fnins.2019.00116
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