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- Title
Identification of rare <italic>RTN3</italic> variants in Alzheimer’s disease in Han Chinese.
- Authors
Zou, Yongyi; He, Wanxia; Wang, Kangli; Han, Hailong; Xiao, Tingting; Chen, Xumeng; Zhou, Bin; Tan, Jieqiong; Xia, Kun; Tang, Beisha; Chen, Chao; Shen, Lu; Yan, Riqiang; Zhang, Zhuohua
- Abstract
Reticulon 3 (RTN3) is a neuronally-expressed reticulon family protein that was previously shown to negatively regulate BACE1, a protease that is required for the generation of β-amyloid peptides (Aβ) from amyloid precursor protein. Despite biochemical and morphological evidence that supports a role of RTN3 in the formation of neuritic amyloid plaques, no systematic analyses of <italic>RTN3</italic> mutations in patients with Alzheimer’s disease (AD) have yet been reported. <italic>RTN3</italic> were targeted sequenced in 154 sporadic early-onset and 285 late-onset AD patients. Luciferase reporter assay and kymographs were performed to analysis the expression of RNT3 and BACE1-RFP particle mobility on cells transfected with wild-type or variants RTN3 constructs. We identified heterozygous variants such as c.-8G > T, c.17C > A, c.42C > T, and c.116C > T from patients in the early-onset AD group and c.-8G > T, c.17C > A, from patients in the late-onset AD group. Such variants of RTN3 were not observed in control individuals. Further biochemical studies show that the <italic>RTN3</italic> c.-8G > T variant in the 5′-untranslated region appears to cause reduced expression of RTN3. The <italic>RTN3</italic> c.116 C > T variant causes a change of codon T39 to M39 (T39 M). Overexpression of RTN3 T39 M in cultured neurons led to impaired axonal transport of BACE1. The variants found in this study are likely genetic modifiers for RTN3-mediated formation of neuritic plaques in AD.
- Subjects
RETICULON proteins; ALZHEIMER'S disease; AMYLOID beta-protein precursor; LUCIFERASE genetics; PROTEOLYTIC enzymes
- Publication
Human Genetics, 2018, Vol 137, Issue 2, p141
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-018-1868-1