. 2015 Oct 2;10(10):e0139082.

doi: 10.1371/journal.pone.0139082. eCollection 2015.

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months

Collaborators, Affiliations

Collaborators

Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Group:
David Ames, Alan Rembach, Stephanie Rainey-Smith, Kathryn Ellis, Lance Macaulay, Ralph Martins, Colin Masters, Christopher Rowe, Arti Appannah, Mary Barnes, Kevin Barnham, Justin Bedo, Shayne Bellingham, Lynette Bon, Pierrick Bourgeat, Belinda Brown, Rachel Buckley, Samantha Burnham, Ashley Bush, Graeme Chandler, Karren Chen, Roger Clarnette, Steven Collins, Ian Cooke, Tiffany Cowie, Kay Cox, Emily Cuningham, Elizabeth Cyarto, Phuong Anh Vu Dang, David Darby, Patricia Desmond, James Doecke, Vincent Dore, Harriet Downing, Belinda Dridan, Konsta Duesing, Michael Fahey, Maree Farrow, Noel Faux, Michael Fenech, Shane Fernandez, Binosha Fernando, Chris Fowler, Maxime Francois, Jurgen Fripp, Shaun Frost, Samantha Gardener, Simon Gibson, Petra Graham, Veer Gupta, David Hansen, Karra Harrington, Andy Hill, Eugene Hone, Maryam Hor, Malcolm Horne, Brenda Huckstepp, Andrew Jones, Gareth Jones, Adrian Kamer, Yogi Kanagasingam, Lisa Keam, Adam Kowalczyk, Betty Krivdic, Chiou Peng Lam, Fiona Lamb, Nicola Lautenschlager, Simon Laws, Wayne Leifert, Nat Lenzo, Hugo Leroux, Falak Lftikhar, Qiao-Xin Li, Florence Lim, Lucy Lim, Linda Lockett, Kathy Lucas, Mark Mano, Caroline Marczak, Georgia Martins, Paul Maruff, Yumiko Matsumoto, Sabine Bird, Simon McBride, Rachel McKay, Rachel Mulligan, Tabitha Nash, Julie Nigro, Graeme O'Keefe, Kevin Ong, Bernadette Parker, Steve Pedrini, Jeremiah Peiffer, Sveltana Pejoska, Lisa Penny, Keyla Perez, Kelly Pertile, Pramit Phal, Tenielle Porter, Stephanie Rainey-Smith, Parnesh Raniga, Alan Rembach, Carolina Restrepo, Malcolm Riley, Blaine Roberts, Jo Robertson, Mark Rodrigues, Alicia Rooney, Rebecca Rumble, Tim Ryan, Olivier Salvado, Mather Samuel, Ian Saunders, Greg Savage, Brendan Silbert, Hamid Sohrabi, Julie Syrette, Cassandra Szoeke, Kevin Taddei, Tania Taddei, Sherilyn Tan, Michelle Tegg, Philip Thomas, Darshan Trivedi, Brett Trounson, Robyn Veljanovski, Giuseppe Verdile, Victor Villemagne, Irene Volitakis, Cassandra Vockler, Michael Vovos, Freda Vrantsidis, Stacey Walker, Andrew Watt, Mike Weinborn, Bill Wilson, Michael Woodward, Olga Yastrubetskaya, Paul Yates, Ping Zhang, Graeme Chandler, Pratishtha Chatterjee, Rhona Creegan, Karl De Ruyck, Hang Ding, Konsta Duesing, Michael Fahey, David Groth, Richard Head, Debra Krause, Rebecca Lachovitzki, Yen Ying Lim, Teresa Lintern, Alinda Mondal, Stewart Nuttall, Nathan O'Callaghan, Lisa Osborne, Chaoyi Pang, Glen Patten, Alison Tuckfield, Jose Varghese, Andrea Wilson, Qing Zhang

Affiliations

¹ Department of Psychology, Royal Melbourne Institute of Technology, Melbourne, Australia.
² The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, United States of America; Department of Neurology, Rhode Island Hospital, Providence, Rhode Island, United States of America.
³ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
⁴ Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia; Co-operative Research Centre for Mental Health, Perth, Western Australia, Australia.
⁵ Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁷ Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
⁸ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁹ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁰ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.

PMID: 26430784
PMCID: PMC4592244
DOI: 10.1371/journal.pone.0139082

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months

Christine Thai et al. PLoS One. 2015.

. 2015 Oct 2;10(10):e0139082.

doi: 10.1371/journal.pone.0139082. eCollection 2015.

Collaborators

Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Group:
David Ames, Alan Rembach, Stephanie Rainey-Smith, Kathryn Ellis, Lance Macaulay, Ralph Martins, Colin Masters, Christopher Rowe, Arti Appannah, Mary Barnes, Kevin Barnham, Justin Bedo, Shayne Bellingham, Lynette Bon, Pierrick Bourgeat, Belinda Brown, Rachel Buckley, Samantha Burnham, Ashley Bush, Graeme Chandler, Karren Chen, Roger Clarnette, Steven Collins, Ian Cooke, Tiffany Cowie, Kay Cox, Emily Cuningham, Elizabeth Cyarto, Phuong Anh Vu Dang, David Darby, Patricia Desmond, James Doecke, Vincent Dore, Harriet Downing, Belinda Dridan, Konsta Duesing, Michael Fahey, Maree Farrow, Noel Faux, Michael Fenech, Shane Fernandez, Binosha Fernando, Chris Fowler, Maxime Francois, Jurgen Fripp, Shaun Frost, Samantha Gardener, Simon Gibson, Petra Graham, Veer Gupta, David Hansen, Karra Harrington, Andy Hill, Eugene Hone, Maryam Hor, Malcolm Horne, Brenda Huckstepp, Andrew Jones, Gareth Jones, Adrian Kamer, Yogi Kanagasingam, Lisa Keam, Adam Kowalczyk, Betty Krivdic, Chiou Peng Lam, Fiona Lamb, Nicola Lautenschlager, Simon Laws, Wayne Leifert, Nat Lenzo, Hugo Leroux, Falak Lftikhar, Qiao-Xin Li, Florence Lim, Lucy Lim, Linda Lockett, Kathy Lucas, Mark Mano, Caroline Marczak, Georgia Martins, Paul Maruff, Yumiko Matsumoto, Sabine Bird, Simon McBride, Rachel McKay, Rachel Mulligan, Tabitha Nash, Julie Nigro, Graeme O'Keefe, Kevin Ong, Bernadette Parker, Steve Pedrini, Jeremiah Peiffer, Sveltana Pejoska, Lisa Penny, Keyla Perez, Kelly Pertile, Pramit Phal, Tenielle Porter, Stephanie Rainey-Smith, Parnesh Raniga, Alan Rembach, Carolina Restrepo, Malcolm Riley, Blaine Roberts, Jo Robertson, Mark Rodrigues, Alicia Rooney, Rebecca Rumble, Tim Ryan, Olivier Salvado, Mather Samuel, Ian Saunders, Greg Savage, Brendan Silbert, Hamid Sohrabi, Julie Syrette, Cassandra Szoeke, Kevin Taddei, Tania Taddei, Sherilyn Tan, Michelle Tegg, Philip Thomas, Darshan Trivedi, Brett Trounson, Robyn Veljanovski, Giuseppe Verdile, Victor Villemagne, Irene Volitakis, Cassandra Vockler, Michael Vovos, Freda Vrantsidis, Stacey Walker, Andrew Watt, Mike Weinborn, Bill Wilson, Michael Woodward, Olga Yastrubetskaya, Paul Yates, Ping Zhang, Graeme Chandler, Pratishtha Chatterjee, Rhona Creegan, Karl De Ruyck, Hang Ding, Konsta Duesing, Michael Fahey, David Groth, Richard Head, Debra Krause, Rebecca Lachovitzki, Yen Ying Lim, Teresa Lintern, Alinda Mondal, Stewart Nuttall, Nathan O'Callaghan, Lisa Osborne, Chaoyi Pang, Glen Patten, Alison Tuckfield, Jose Varghese, Andrea Wilson, Qing Zhang

Affiliations

¹ Department of Psychology, Royal Melbourne Institute of Technology, Melbourne, Australia.
² The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, United States of America; Department of Neurology, Rhode Island Hospital, Providence, Rhode Island, United States of America.
³ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
⁴ Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia; Co-operative Research Centre for Mental Health, Perth, Western Australia, Australia.
⁵ Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia; National Ageing Research Institute, Parkville, Victoria, Australia.
⁷ Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia, Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
⁸ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
⁹ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁰ The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.

PMID: 26430784
PMCID: PMC4592244
DOI: 10.1371/journal.pone.0139082

Abstract

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: Christine Thai, Yen Ying Lim, Kathryn A. Ellis, Stephanie R. Rainey-Smith and Simon M. Laws report no relevant disclosures. Colin L. Masters is an advisor to Prana Biotechnology Ltd and a consultant to Eli Lilly. R. H. P. is a scientific consultant to Cogstate Ltd. Paul Maruff is a full-time employee of Cogstate Ltd. David Ames has served on scientific advisory boards for Novartis, Eli Lilly, Janssen, and Pfizer Inc. Ralph N. Martins is a consultant to Alzhyme. Christopher C. Rowe has served on scientific advisory boards for Bayer Pharma, Elan Corporation, GE Healthcare and AstraZeneca; has received speaker honoraria from Bayer Pharma and GE Healthcare; and has received research support from Bayer Pharma, GE Healthcare, Piramal Lifesciences and Avid Radiopharmaceuticals. Victor L. Villemagne served as a consultant for Bayer Pharma; and received research support from a NEDO grant from Japan. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

**Fig 1. Magnitude of difference for cognitive decline over 18 months, relative to the Aβ- ε4 non-carrier group.**
0 line represents the Aβ- ε4 non-carrier group; error bars represent 95% confidence intervals. *p<.05.

See this image and copyright information in PMC

References

1. Corder E, Saunders A, Strittmatter W, Schmechel D, Gaskell P, Small GW, et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261: 921–923. - PubMed
1. Small BJ, Rosnick CB, Fratiglioni L, Bäckman L (2004) Apolipoprotein E and cognitive performance: a meta-analysis. Psychology and aging 19: 592 - PubMed
1. Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, et al. (2011) Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Annals of neurology 69: 181–192. 10.1002/ana.22248 - DOI - PMC - PubMed
1. Chetelat G, Villemagne VL, Bourgeat P, Pike KE, Jones G, Ames D, et al. (2010) Relationship between atrophy and β‐amyloid deposition in Alzheimer disease. Annals of neurology 67: 317–324. 10.1002/ana.21955 - DOI - PubMed
1. Villemagne V, Pike K, Darby D, Maruff P, Savage G, Ng S, et al. (2008) Aβ deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease. Neuropsychologia 46: 1688–1697. 10.1016/j.neuropsychologia.2008.02.008 - DOI - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months

Collaborators

Affiliations

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous