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

Research output: Contribution to journalArticle

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.

LanguageEnglish
Article number2034
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

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Amyloid
Atrophy
Alleles
Genotype
Episodic Memory
Cognition
Single Nucleotide Polymorphism
Alzheimer Disease
Observation
Kidney
Cognitive Dysfunction
Brain
Proteins

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Porter, Tenielle ; Burnham, Samantha C. ; Doré, Vincent ; Savage, Greg ; Bourgeat, Pierrick ; Begemann, Kimberly ; Milicic, Lidija ; Ames, David ; Bush, Ashley I. ; Maruff, Paul ; Masters, Colin L. ; Rowe, Christopher C. ; Rainey-Smith, Stephanie ; Martins, Ralph N. ; Groth, David ; Verdile, Giuseppe ; Villemagne, Victor L. ; Laws, Simon M./ KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ϵ4-positive cognitively normal adults with high Aβ-amyloid burden. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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.",
author = "Tenielle Porter and Burnham, {Samantha C.} and Vincent Dor{\'e} and Greg Savage and Pierrick Bourgeat and Kimberly Begemann and Lidija Milicic and David Ames and Bush, {Ashley I.} and Paul Maruff and Masters, {Colin L.} and Rowe, {Christopher C.} and Stephanie Rainey-Smith and Martins, {Ralph N.} and David Groth and Giuseppe Verdile and Villemagne, {Victor L.} and Laws, {Simon M.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-20513-y",
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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 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, vol 8, no. 1, 2034. DOI: 10.1038/s41598-018-20513-y

KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ϵ4-positive cognitively normal adults with high Aβ-amyloid burden. / Porter, Tenielle; Burnham, Samantha C.; Doré, Vincent; Savage, Greg; Bourgeat, Pierrick; Begemann, Kimberly; Milicic, Lidija; Ames, David; Bush, Ashley I.; Maruff, Paul; Masters, Colin L.; Rowe, Christopher C.; Rainey-Smith, Stephanie; Martins, Ralph N.; Groth, David; Verdile, Giuseppe; Villemagne, Victor L.; Laws, Simon M.

In: Scientific Reports, Vol. 8, No. 1, 2034, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ϵ4-positive cognitively normal adults with high Aβ-amyloid burden

AU - Porter,Tenielle

AU - Burnham,Samantha C.

AU - Doré,Vincent

AU - Savage,Greg

AU - Bourgeat,Pierrick

AU - Begemann,Kimberly

AU - Milicic,Lidija

AU - Ames,David

AU - Bush,Ashley I.

AU - Maruff,Paul

AU - Masters,Colin L.

AU - Rowe,Christopher C.

AU - Rainey-Smith,Stephanie

AU - Martins,Ralph N.

AU - Groth,David

AU - Verdile,Giuseppe

AU - Villemagne,Victor L.

AU - Laws,Simon M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

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