KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ε4-positive cognitively normal adults with high Aβ-amyloid burden.
KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ε4-positive cognitively normal adults with high Aβ-amyloid burden.
复制标题
DOI：
10.1038/s41598-018-20513-y
复制
发表时间：
2018-02-01
影响因子：
4.6
通讯作者：
Laws SM
中科院分区：
文献类型：
--
作者：
Porter T;Burnham SC;Doré V;Savage G;Bourgeat P;Begemann K;Milicic L;Ames D;Bush AI;Maruff P;Masters CL;Rowe CC;Rainey-Smith S;Martins RN;Groth D;Verdile G;Villemagne VL;Laws SM
KIdney和BRAin表达蛋白（KIBRA）基因中的单核苷酸多态性rs 17070145与认知正常（CN）个体的认知和海马体积相关。然而，rs 17070145对发展为阿尔茨海默病的最大风险的CN成年人的纵向认知下降和海马萎缩的影响尚不清楚。我们研究了rs 17070145对602名CN成年人6年内认知能力下降和海马萎缩率的影响，已知脑Aβ-淀粉样蛋白水平，以及是否与APOE基因型存在交互作用。我们发现，虽然观察到KIBRA基因型的独立影响有限，但在整个研究期间，在Aβ-淀粉样蛋白水平较高的CN成人中，APOE存在相互作用。与携带rs 17070145-T等位基因的APOE ε4-ve个体相比，在APOE ε4 + ve且不携带rs 17070145-T等位基因的个体中观察到认知下降（全局，p = 0.006;言语情景记忆，p = 0.004）和海马萎缩（p = 0.04）的速率显著更快。在高Aβ-淀粉样蛋白存在下，仅在rs 17070145-T等位基因非携带者中观察到APOE效应，表明rs 17070145-T等位基因携带者对高Aβ-淀粉样蛋白和APOE ε4的有害作用具有一定程度的恢复力。
A single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein (KIBRA) gene has been associated with cognition and hippocampal volume in cognitively normal (CN) individuals. However, the impact of rs17070145 on longitudinal cognitive decline and hippocampal atrophy in CN adults at greatest risk of developing Alzheimer’s disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippocampal atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype. We reveal that whilst limited independent effects of KIBRA genotype were observed, there was an interaction with APOE in CN adults who presented with high Aβ-amyloid levels across study duration. In comparison to APOE ε4-ve individuals carrying the rs17070145-T allele, significantly faster rates of cognitive decline (global, p = 0.006; verbal episodic memory, p = 0.004), and hippocampal atrophy (p = 0.04) were observed in individuals who were APOE ε4 + ve and did not carry the rs17070145-T allele. The observation of APOE effects in only non-carriers of the rs17070145-T allele, in the presence of high Aβ-amyloid suggest that carriers of the rs17070145-T allele are conferred a level of resilience to the detrimental effects of high Aβ-amyloid and APOE ε4.
登录
查看更多内容
影响因子：
3.7
作者：
Andrews KA;Modat M;Macdonald KE;Yeatman T;Cardoso MJ;Leung KK;Barnes J;Villemagne VL;Rowe CC;Fox NC;Ourselin S;Schott JM;Australian Imaging Biomarkers, Lifestyle Flagship Study of Ageing
通讯作者：
Australian Imaging Biomarkers, Lifestyle Flagship Study of Ageing
影响因子：
--
作者：
Gueorguieva, R;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
9.9
作者：
Derby, Carol A.;Burns, Leah C.;Lipton, Richard B.
通讯作者：
Lipton, Richard B.
影响因子：
4.2
作者：
Lim, Yen Ying;Villemagne, Victor L.;Maruff, Paul
通讯作者：
Maruff, Paul
影响因子：
2.9
作者：
Kennedy, Kristen M.;Reese, Elizabeth D.;Horn, Marci M.;Sizemore, April N.;Unni, Asha K.;Meerbrey, Michael E.;Kalich, Allan G., Jr.;Rodrigue, Karen M.
通讯作者：
Rodrigue, Karen M.