Impact of PICALM and CLU on hippocampal degeneration

Yang, Xianfeng, Li, Jin, Liu, Bing, Li, Yonghui and Jiang, Tianzi (2016) Impact of PICALM and CLU on hippocampal degeneration. Human Brain Mapping, 37 7: 2419-2430. doi:10.1002/hbm.23183


Author Yang, Xianfeng
Li, Jin
Liu, Bing
Li, Yonghui
Jiang, Tianzi
Title Impact of PICALM and CLU on hippocampal degeneration
Formatted title
Impact of PICALM and CLU on hippocampal degeneration
Journal name Human Brain Mapping   Check publisher's open access policy
ISSN 1097-0193
1065-9471
Publication date 2016-07-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/hbm.23183
Open Access Status Not yet assessed
Volume 37
Issue 7
Start page 2419
End page 2430
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
PICALM and CLU are two major risk genes of late-onset Alzheimer's disease (LOAD), and there is strong molecular evidence suggesting their interaction on amyloid-beta deposition, hence finding functional dependency between their risk genotypes may lead to better understanding of their roles in LOAD development and greater clinical utility. In this study, we mainly investigated interaction effects of risk loci PICALM rs3581179 and CLU rs11136000 on hippocampal degeneration in both young and elderly adults in order to understand their neural mechanism on aging process, which may help identify robust biomarkers for early diagnosis and intervention. Besides volume we also assessed hippocampal shape phenotypes derived from diffeomorphic metric mapping and nonlinear dimensionality reduction. In elderly individuals (75.6 ± 6.7 years) significant interaction effects existed on hippocampal volume (P < 0.001), whereas in young healthy adults (19.4 ± 1.1 years) such effects existed on a shape phenotype (P = 0.01) indicating significant variation at hippocampal head and tail that mirror most AD vulnerable regions. Voxel-wise analysis also pointed to the same regions but lacked statistical power. In both cohorts, PICALM protective genotype AA only exhibited protective effects on hippocampal degeneration and cognitive performance when combined with CLU protective T allele, but adverse effects with CLU risk CC. This study revealed novel PICALM and CLU interaction effects on hippocampal degeneration along aging, and validated effectiveness of diffeomorphometry in imaging genetics study.
Keyword Alzheimer's disease
CLU
Hippocampus
Interaction
PICALM
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
 
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