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

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

School of Psychological Science

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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) 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). Conclusion: 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 language	English
Pages (from-to)	111-120
Number of pages	10
Journal	Journal of Alzheimer's Disease Reports
Volume	5
Issue number	1
DOIs	https://doi.org/10.3233/ADR-200246
Publication status	Published - 2021

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Fernandez, S., Burnham, S. C., Milicic, L., Savage, G., Maruff, P., Peretti, M., Sohrabi, H. R., 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., & 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), 111-120. https://doi.org/10.3233/ADR-200246

@article{0fa27a82e7dc4098a6e14d0b6ad98c77,

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

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) 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). Conclusion: 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.",

keywords = "Alzheimer's disease, amyloid-β, APOE, cognitive decline, SPON1, Spondin-1",

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

year = "2021",

doi = "10.3233/ADR-200246",

language = "English",

volume = "5",

pages = "111--120",

journal = "Journal of Alzheimer's Disease Reports",

issn = "2542-4823",

publisher = "IOS Press",

number = "1",

}

Fernandez, S, Burnham, SC, Milicic, L, Savage, G, Maruff, P, Peretti, M, Sohrabi, HR, Lim, YY, Weinborn, M, Ames, D, Masters, CL, Martins, RN, Rainey-Smith, S, Rowe, CC, Salvado, O, Groth, D, Verdile, G, Villemagne, VL, Porter, T & Laws, SM 2021, 'SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults', Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 111-120. https://doi.org/10.3233/ADR-200246

TY - JOUR

T1 - SPON1 Is Associated with Amyloid-β and APOE ϵ4-Related Cognitive Decline in Cognitively Normal Adults

AU - Fernandez, Shane

AU - Burnham, Samantha C.

AU - Milicic, Lidija

AU - Savage, Greg

AU - Maruff, Paul

AU - Peretti, Madeline

AU - Sohrabi, Hamid R.

AU - Lim, Yen Ying

AU - Weinborn, Michael

AU - Ames, David

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - Rainey-Smith, Stephanie

AU - Rowe, Christopher C.

AU - Salvado, Olivier

AU - Groth, David

AU - Verdile, Giuseppe

AU - Villemagne, Victor L.

AU - Porter, Tenielle

AU - Laws, Simon M.

PY - 2021

Y1 - 2021

N2 - 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) 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). Conclusion: 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.

AB - 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) 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). Conclusion: 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.

KW - Alzheimer's disease

KW - amyloid-β

KW - APOE

KW - cognitive decline

KW - SPON1

KW - Spondin-1

UR - http://www.scopus.com/inward/record.url?scp=85105689483&partnerID=8YFLogxK

U2 - 10.3233/ADR-200246

DO - 10.3233/ADR-200246

M3 - Article

C2 - 33782664

AN - SCOPUS:85105689483

SN - 2542-4823

VL - 5

SP - 111

EP - 120

JO - Journal of Alzheimer's Disease Reports

JF - Journal of Alzheimer's Disease Reports

IS - 1

ER -

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

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