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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review



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


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) ϵ4 and rs11023139 in individuals with high amyloid-β burden. APOE ϵ4/rs11023139-A carriers declined significantly faster than APOE ϵ4/rs11023139-G-G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020). 


These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ϵ4 cognitively normal older adults with a high neocortical amyloid-β burden.

Original languageEnglish
Pages (from-to)111-120
Number of pages10
JournalJournal of Alzheimer's disease reports
Issue number1
Publication statusPublished - 24 Feb 2021

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Alzheimer's disease
  • amyloid-β
  • 𝘈𝘗𝘖𝘌
  • cognitive decline
  • 𝘚𝘗𝘖𝘕1
  • Spondin-1

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