AUTHOR=Tan Mengshan , Li Jieqiong , Ma Fangchen , Zhang Xing , Zhao Qingfei , Cao Xipeng 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.00116

DOI=10.3389/fnins.2019.00116

ISSN=1662-453X

ABSTRACT=<p>Next-generation sequencing studies have reported that rare variants in <italic>PLD3</italic> 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 <italic>PLD3</italic> 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.</p>