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^*

^*Corresponding author for this work

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

3 Citations (Scopus)

33 Downloads (Pure)

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 - 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.

Keywords

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

Access to Document

10.3233/ADR-200246Licence: CC BY-NC

Publisher version (open access)Final published version, 548 KBLicence: CC BY-NC

Cite this

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{87ae9b92b72b4a7696fa18be59120474,

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.}",

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.",

year = "2021",

month = feb,

day = "24",

doi = "10.3233/ADR-200246",

language = "English",

volume = "5",

pages = "111--120",

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

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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.

N1 - 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.

PY - 2021/2/24

Y1 - 2021/2/24

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

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DO - 10.3233/ADR-200246

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AN - SCOPUS:85105689483

SN - 2542-4823

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JO - Journal of Alzheimer's Disease Reports

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