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Title: KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ε4-positive cognitively normal adults with high Aβ-amyloid burden.
Austin Authors: 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 R;Martins, Ralph N;Groth, David;Verdile, Giuseppe;Villemagne, Victor L ;Laws, Simon M
Affiliation: Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, 6027, Western Australia, Australia
Co-operative Research Centre for Mental Health, Carlton South, 3053 Victoria, Australia
CSIRO Health and Biosecurity, Parkville, 3052, Victoria, Australia
Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, 6027, Western Australia, Australia
eHealth, CSIRO Health and Biosecurity, Herston, 4029, QLD, Australia
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, North Ryde, 2113, NSW, Australia
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, 3101, Victoria, Australia
National Ageing Research Institute, Parkville, 3052, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3052, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, 6009, Western Australia, Australia
School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, 6102, Western Australia, Australia
CogState Ltd., Melbourne, 3000, Victoria, Australia
Issue Date: Feb-2018 2018-02-01
Publication information: Scientific Reports 2018; 8(1): 2034
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.
DOI: 10.1038/s41598-018-20513-y
ORCID: 0000-0001-8259-9069
PubMed URL: 29391469
Type: Journal Article
Appears in Collections:Journal articles

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