KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ϵ4-positive cognitively normal adults with high Aβ-amyloid burden

Tenielle Porter, Samantha C. Burnham, Vincent Doré, Greg Savage, Pierrick Bourgeat, Kimberly Begemann, Lidija Milicic, David Ames, Ashley I. Bush, Paul Maruff, Colin L. Masters, Christopher C. Rowe, Stephanie Rainey-Smith, Ralph N. Martins, David Groth, Giuseppe Verdile, Victor L. Villemagne, Simon M. Laws

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Abstract

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.

Original languageEnglish
Article number2034
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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    Porter, T., Burnham, S. C., Doré, V., Savage, G., Bourgeat, P., Begemann, K., Milicic, L., Ames, D., Bush, A. I., Maruff, P., Masters, C. L., Rowe, C. C., Rainey-Smith, S., Martins, R. N., Groth, D., Verdile, G., Villemagne, V. L., & Laws, S. M. (2018). KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ϵ4-positive cognitively normal adults with high Aβ-amyloid burden. Scientific Reports, 8(1), [2034]. https://doi.org/10.1038/s41598-018-20513-y