SPON1 Is Associated with Amyloid-β and APOE ε4-Related Cognitive Decline in Cognitively Normal Adults

Shane Fernandez; Samantha C Burnham; Lidija Milicic; Greg Savage; Paul Maruff; Madeline Peretti; Hamid R Sohrabi; Yen Ying Lim; Michael Weinborn; David Ames; Colin L Masters; Ralph N Martins; Stephanie Rainey-Smith; Christopher C Rowe; Olivier Salvado; David Groth; Giuseppe Verdile; Victor L Villemagne; Tenielle Porter; Simon M Laws

doi:10.3233/ADR-200246

SPON1 Is Associated with Amyloid-β and APOE ε4-Related Cognitive Decline in Cognitively Normal Adults

J Alzheimers Dis Rep. 2021 Feb 24;5(1):111-120. doi: 10.3233/ADR-200246.

Authors

Shane Fernandez^{1

2}, Samantha C Burnham^{2

3}, Lidija Milicic², Greg Savage⁴, Paul Maruff^{5

6}, Madeline Peretti², Hamid R Sohrabi^{1

7

8

9}, Yen Ying Lim¹⁰, Michael Weinborn^{1

9

11}, David Ames^{12

13}, Colin L Masters⁵, Ralph N Martins^{1

8

9}, Stephanie Rainey-Smith^{1

9}, Christopher C Rowe^{14

15}, Olivier Salvado¹⁶, David Groth¹⁷, Giuseppe Verdile^{9

17}, Victor L Villemagne^{2

14}, Tenielle Porter^{2

17}, Simon M Laws^{2

17}

Affiliations

¹ Australian Alzheimer's Research Foundation, Nedlands, Western Australia.
² Collaborative Genomics and Translation Group, Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
³ CSIRO Health and Biosecurity, Parkville, Victoria, Australia.
⁴ ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, North Ryde, NSW, Australia.
⁵ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
⁶ CogState Ltd., Melbourne, Victoria, Australia.
⁷ Centre for Healthy Ageing, Murdoch University, Murdoch, Western Australia, Australia.
⁸ Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁹ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
¹⁰ Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
¹¹ School of Psychological Science, University of Western Australia, Crawley, Western Australia, Australia.
¹² Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia.
¹³ National Ageing Research Institute, Parkville, Victoria, Australia.
¹⁴ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
¹⁵ Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
¹⁶ CSIRO Health and Biosecurity/Australian e-Health Research Centre, Herston, Queensland, Australia.
¹⁷ School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia.

Abstract

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease.

Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults.

Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study.

Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ɛ4 and rs11023139 in individuals with high amyloid-β burden. APOE ɛ4/rs11023139-A carriers declined significantly faster than APOE ɛ4/rs11023139-G_G carriers in measures of global cognition (p = 0.011) and verbal episodic memory (p = 0.020).

Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ɛ4 cognitively normal older adults with a high neocortical amyloid-β burden.

Keywords: APOE; Alzheimer’s disease; SPON1; Spondin-1; amyloid-β; cognitive decline.