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SPON1 Is associated with Amyloid-β and APOE ε4-Related cognitive decline in cognitively normal adults

Fernandez, S., Burnham, S.C., Milicic, L., Savage, G., Maruff, P., Peretti, M., Sohrabi, H.R.ORCID: 0000-0001-8017-8682, Lim, Y.Y., Weinborn, M., Ames, D., Masters, C.L., Martins, R.N., Rainey-Smith, S., Rowe, C.C., Salvado, O., Groth, D., Verdile, G., Villemagne, V.L., Porter, T. and Laws, S.M. (2021) SPON1 Is associated with Amyloid-β and APOE ε4-Related cognitive decline in cognitively normal adults. Journal of Alzheimer's Disease Reports, 5 (1). pp. 111-120.

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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.


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.


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).


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.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Healthy Ageing
Publisher: IOS Press
Copyright: © 2021 The Authors.
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